Amide derivatives

ABSTRACT

A medicament for enhancing an effect of a cancer therapy based on a mode of action of DNA injury, which comprises as an active ingredient a compound represented by the following general formula (I) or a salt thereof: 
                         
wherein one of R 1  and R 2  represents hydrogen atom and the other represents the formula —X-A wherein A represents hydrogen atom or an acyl group, X represents oxgen atom or NH; one of R 3  and R 4  represents hydrogen atom and the other represents the following formula:
 
                         
wherein Y represents a sulfonyl group or a carbonyl group, R 5  represents a cyclic group, Z represents a single bond or a C 1  to C 4  alkylene group, R 6  represents hydrogen atom or a C 1  to C 6  alkyl group.

FIELD OF INVENTION

The present invention relates to medicaments for enhancing the effect ofcancer therapy on the basis of mechanism of injuring DNA, and novelcompounds useful as active ingredients of said medicament.

BACKGROUND ART

Anticancer agents are administered in treatments of cancer patients atpresent. However, their life-prolongation rates are undesirably low, andmoreover, cancer patients administered with an anticancer agent areforced to tolerate severe side effects such as fever, nausea, epilation,chill, fatigue, immune malfunction, gastrointestinal disorder, liverdisorder, and kidney disorder, which becomes a cause of significantdeterioration of the QOL (Quality of Life) of the cancer patients.Furthermore, reduction of sensitivity of cancer cells to anticanceragents, caused by the use of the anticancer agents, may lead toprolonged administration period of administration of the anticanceragents and increase of doses, and as a result, deaths resulting fromside effects of the anticancer agents are often observed. Therefore, theadministration of anticancer agents may spoil advantages of patients, aswell as significantly diminish social and economic benefits. This iscaused by the fact that anticancer agents, which are expectedly used toexhibit selective cytotoxicity to cancer cells that disorderly divideand proliferate, actually act cytotoxically on normal cells,particularly on cells in the intestine and marrow.

In recent years, reports have been made on caffeine which is a lowmolecule organic compound and UCN-01(7-hydroxy staurosporine) havingactions to enhance radiation susceptibility of cancer cells which areradiation resistant (J. Biol. Chem., 275, 5600-5605, 2000; J. Biol.Chem., 276, 17693-17698, 2001). Cancer therapy by radiation is alsobased on the mode of action of artificial injury of DNAs, and isconsidered to be basically equivalent to anticancer agents such asbleomycin based on the mode of action of DNA injury. Accordingly, it isbelieved that a drug that enhances selective toxicity to cancer cellscan be developed even for anticancer agents based on the mode of actionof DNA injury which are available at present.

In fact, it is reported that caffeine increases the actions ofanticancer agents such as adriamycin, cisplatin, cyclophosphamide, andmitomycin C based on the mode of action of DNA injury (Jpn. J. Cancer.Res., 80, 83-88, 1989). However, potency remains insufficient, andseparation from toxicity is unsatisfactory. UCN-01 is also reported toenhance actions of several kinds of anticancer agents based on the modeof action of DNA injury (Invest. New Drugs, 18, 95-107, 2000).

As for the mode of action of the potentiation of anticancer agents, theaction is presumed to be based on a destruction of a certain part of thecell cycle (for example, G1 period and G2 period: Cancer Res., 60,2108-2112, 2000; Cancer Res., 59, 4375-4382(1999), since caffeine andUCN-01 inhibit protein kinases involved in a control of a cell cycle (J.Biol. Chem., 275, 10342-10348, 2000; Cancer Res., 61, 1065-1072, 2001).However, no conclusive evidence has been obtained. In addition, sincecaffeine and UNC-01 as a staurosporin derivative have inhibitory actionsagainst multiple kinds of protein kinases (Biochem. Biophys. Res.Commun., 219, 778-783, 1996; Acta Pharmacol. Sin., 21, 35-40, 2000), apossibility of involvement of a mechanism other than the destruction ofthe cell cycle can not be denied. Accordingly, a clear mode of actionremains unidentified. Furthermore, there is a high possibility thatthese agents have inhibitory actions also against protein kinasesparticipating in intracellular signal transduction, which is consideredto be a possible cause of inducing serious side effects.

As explained above, no effective means is available at present to solvevarious problems caused by the cancer therapies based on the mode ofaction of DNA injury. Developments of new drugs or therapies, thatpotentiate the effects of available anticancer agents and radiationtherapy based on the mode of action of DNA injury and that enhanceselectivity to cancer cells to decrease side effects, will contribute toincrease the QOL and advantages of cancer patients as well as social andeconomic benefits.

DISCLOSURE OF THE INVENTION

An object of the present invention is to provide medicaments forenhancing the effect of cancer therapy based on the mode of action ofDNA injury. More specifically, an object of the present invention is toprovide medicaments which, per se, have weak anticancer activity(cytotoxicity), but in combination of an anticancer agent based on themode of action of DNA injury or a therapy such as radiation which givesartificial injuries to DNA, can selectively damage or kill cancer cellsat a lower dose of anticancer agent or a lower radiation dose so as tosignificantly reduce affects on normal cells. Furthermore, anotherobject of the present invention is to provide medicaments to reduce sideeffects resulting from cancer therapy by potentiation of the effects ofthe above cancer therapy and by reduction of a dose of the anticanceragent and/or radiation dose. Still further object of the presentinvention is to provide novel compounds which are useful as activeingredients of the above medicaments.

The inventors of the present invention focused on protein kinaseinhibitors to solve the aforementioned objects, and carried out searchfor compounds having desired pharmacological activities by usingcomputerized molecular design technology as a means to discovercandidate compounds. The inventors carried out an automatic searchprogram of a ligand from a three-dimensional compound database based onthe three-dimensional structure of the protein by using the ATP bindingregions of several kinds of protein kinases whose structures areregistered in PDB (Protein Data Bank), and by virtual screenings, theyselected compounds having potentials as protein kinase inhibitors fromcompounds registered in databases of commercial compounds. The inventorsclassified the resulting compounds on the basis of their skeletons, andby using several typical compounds, they carried out tests of combinedeffects with bleomycin on cancer cells and normal cells and tests ofcytotoxicity to cancer cells and normal cells when the compounds areused alone. The inventors selected compounds having strong and desiredpharmacological activities, and further prepared their derivatives toachieve the present invention.

The present invention thus provides a medicament for enhancing an effectof a cancer therapy based on a mode of action of DNA injury whichcomprises as an active ingredient a substance selected from the groupconsisting of a compound represented by the following general formula(I) and a pharmacologically acceptable salt thereof, and a hydratethereof and a solvate thereof:

wherein one of R¹ and R² represents hydrogen atom and the otherrepresents the formula —X-A wherein A represents hydrogen atom or anacyl group, X represents oxygen atom or NH; one of R³ and R⁴ representshydrogen atom and the other represents the following formula:

wherein Y represents a sulfonyl group or a carbonyl group, R⁵ representsa cyclic group which may be substituted, Z represents a single bond or aC₁ to C₄ alkylene group which may be substituted, or when Z issubstituted, said substituent may bind to R⁵ to form a ring group, R⁶represents hydrogen atom or a C₁ to C₆ alkyl group which may besubstituted, or R⁶ may bind to Z or R⁵ to form a cyclic group, providedthat the compound represented by the following formula:

wherein each of A, Z, R⁵ and R⁵ has the same meaning as that definedabove is excluded.

According to preferred embodiments of the aforementioned invention,provided are the aforementioned medicament wherein R⁵ is an aromaticring group which may be substituted; the aforementioned medicamentwherein Z is a methylene group which may be substituted, or when Z issubstituted, said substituent may bind to R⁵ to form a ring group; theaforementioned medicament wherein Y is a sulfonyl group; and theaforementioned medicament wherein R¹ is a group represented by theformula —O-A wherein A represents hydrogen atom or an acyl group, and R²is hydrogen atom.

Furthermore, according to preferred embodiments of the aforementionedinvention, provided are the aforementioned medicament wherein the cancertherapy based on the mode of action of DNA injury is carried out byadministration of an anticancer agent and/or radiation; theaforementioned medicament wherein the anticancer agent is selected froma group consisting of bleomycin, adriamycin, cisplatin,cyclophosphamide, mitomycin C, and their derivatives; and theaforementioned medicament which is a specific inhibitor against aprotein kinase and/or its analogous enzyme.

From another aspect, the present invention provides a medicament forreducing a side effect resulting from a cancer therapy based on the modeof action of DNA injury which comprises as an active ingredient acompound represented by the aforementioned general formula (I) or aphysiologically acceptable salt thereof.

From further another aspect, the present invention provides use of thecompound represented by the aforementioned general formula (I) or thephysiologically acceptable salt thereof for manufacture of theaforementioned medicament; a method of enhancing an effect of cancertherapy based on the mode of action of DNA injury in a mammal includinga human, which comprises the step of applying a cancer therapy based onthe mode of action of DNA injury to a cancer patient, and the step ofadministering the compound represented by the aforementioned generalformula (I) or the physiologically acceptable salt thereof at a dosesufficient to potentiate the effect of the aforementioned cancertherapy; a method of reducing a side effect resulting from a cancertherapy based on the mode of action of DNA injury in a mammal includinga human, which comprises the step of applying a cancer therapy based onthe mode of action of DNA injury to a cancer patient, and the step ofadministering the compound represented by the aforementioned generalformula (I) or the physiologically acceptable salt thereof at a dosesufficient to reduce the side effect of the aforementioned cancertherapy.

Furthermore, the present invention provides a compound represented bythe aforementioned general formula (I) or a pharmacologically acceptablesalt thereof, or a hydrate thereof or a solvate thereof, provided thatthe following compound is excluded.

BEST MODE FOR CARRYING OUT THE INVENTION

The terms used in the present specification have the following meanings.

As the halogen atom, any of fluorine atom, chlorine atom, bromine atom,or iodine atom may be used unless otherwise specifically referred to.

Examples of the hydrocarbon group include, for example, an aliphatichydrocarbon group, an aryl group, an arylene group, an aralkyl group, abridged cyclic hydrocarbon group, a spiro cyclic hydrocarbon group, anda terpene hydrocarbon.

Examples of the aliphatic hydrocarbon group include, for example, alkylgroup, alkenyl group, alkynyl group, alkylene group, alkenylene group,alkylidene group and the like which are straight chain or branched chainmonovalent or bivalent acyclic hydrocarbon groups; cycloalkyl group,cycloalkenyl group, cycloalkanedienyl group, cycloalkyl-alkyl group,cycloalkylene group, and cycloalkenylene group, which are saturated orunsaturated monovalent or bivalent alicyclic hydrocarbon groups.

Examples of the alkyl group include, for example, methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl,isopentyl, 2-methylbutyl, 1-methylbutyl, neopentyl, 1,2-dimethylpropyl,1-ethylpropyl, n-hexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl,1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl,1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 2-ethylbutyl,1-ethylbutyl, 1-ethyl-1-methylpropyl, n-heptyl, n-octyl, n-nonyl,n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, andn-pentadecyl, which are C₁ to C₁₅ straight chain or branched chain alkylgroups.

Examples of the alkenyl group include, for example, vinyl,prop-1-en-1-yl, allyl, isopropenyl, but-1-en-1-yl, but-2-en-1-yl,but-3-en-1-yl, 2-methylprop-2-en-1-yl, 1-methylprop-2-en-1-yl,pent-1-en-1-yl, pent-2-en-1-yl, pent-3-en-1-yl, pent-4-en-1-yl,3-methylbut-2-en-1-yl, 3-methylbut-3-en-1-yl, hex-1-en-1-yl,hex-2-en-1-yl, hex-3-en-1-yl, hex-4-en-1-yl, hex-5-en-1-yl,4-methylpent-3-en-1-yl, 4-methylpent-3-en-1-yl, hept-1-en-1-yl,hept-6-en-1-yl, oct-1-en-1-yl, oct-7-en-1-yl, non-1-en-1-yl,non-8-en-1-yl, dec-1-en-1-yl, dec-9-en-1-yl, undec-1-en-1-yl,undec-10-en-1-yl, dodec-1-en-1-yl, dodec-11-en-1-yl, tridec-1-en-1-yl,tridec-12-en-1-yl, tetradec-1-en-1-yl, tetradec-13-en-1-yl,pentadec-1-en-1-yl, and pentadec-14-en-1-yl, which are C₂ to C₁₅straight chain or branched chain alkenyl groups.

Examples of the alkynyl group include, for example, ethynyl,prop-1-yn-1-yl, prop-2-yn-1-yl, but-1-yn-1-yl, but-3-yn-1-yl,1-methylprop-2-yn-1-yl, pent-1-yn-1-yl, pent-4-yn-1-yl, hex-1-yn-1-yl,hex-5-yn-1-yl, hept-1-yn-1-yl, hept-6-yn-1-yl, oct-1-yn-1-yl,oct-7-yn-1-yl, non-1-yn-1-yl, non-8-yn-1-yl, dec-1-yn-1-yl,dec-9-yn-1-yl, undec-1-yn-1-yl, undec-10-yn-1-yl, dodec-1-yn-1-yl,dodec-11-yn-1-yl, tridec-1-yn-1-yl, tridec-12-yn-1-yl,tetradec-1-yn-1-yl, tetradec-13-yn-1-yl, pentadec-1-yn-1-yl, andpentadec-14-yn-1-yl, which are C₂ to C₁₅ straight chain or branchedchain alkynyl groups.

Examples of the alkylene group include, for example, methylene,ethylene, ethane-1,1-diyl, propane-1,3-diyl, propane-1,2-diyl,propane-2,2-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl,and 1,1,4,4-tetramethylbutane-1,4-diyl group, which are C₁ to C₈straight chain or branched chain alkylene groups.

Examples of the alkenylene group include, for example, ethene-1,2-diyl,propene-1,3-diyl, but-1-ene-1,4-diyl, but-2-ene-1,4-diyl,2-methylpropene-1,3-diyl, pent-2-ene-1,5-diyl, and hex-3-ene-1,6-diyl,which are C₁ to C₆ straight chain or branched chain alkylene groups.

Examples of the alkylidene group include, for example, methylidene,ethylidene, propylidene, isopropylidene, butylidene, pentylidene, andhexylidene, which are C₁ to C₆ straight chain or branched chainalkylidene groups.

Examples of the cycloalkyl group include, for example, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl, whichare C₃ to C₈ cycloalkyl groups. The aforementioned cycloalkyl group maybe fused with benzene ring, naphthalene ring and the like, and examplesinclude, for example, 1-indanyl, 2-indanyl,1,2,3,4-tetrahydronaphthalen-1-yl, and1,2,3,4-tetrahydronaphthalen-2-yl.

Examples of the cycloalkenyl group include, for example,2-cyclopropen-1-yl, 2-cyclobuten-1-yl, 2-cyclopenten-1-yl,3-cyclopenten-1-yl, 2-cyclohexen-1-yl, 3-cyclohexen-1-yl,1-cyclobuten-1-yl, and 1-cyclopenten-1-yl, which are C₃ to C₆cycloalkenyl groups. The aforementioned cycloalkenyl group may be fusedwith benzene ring, naphthalene ring and the like, and examples include,for example, 1-indanyl, 2-indanyl, 1,2,3,4-tetrahydronaphthalen-1-yl,1,2,3,4-tetrahydronaphthalen-2-yl, 1-indenyl, and 2-indenyl.

Examples of the cycloalkanedienyl group include, for example,2,4-cyclopentadien-1-yl, 2,4-cyclohexanedien-1-yl, and2,5-cyclohexanedien-1-yl, which are C₅ to C₆ cycloalkanedienyl groups.The aforementioned cycloalkanedienyl group may be fused with benzenering, naphthalene ring and the like, and examples include, for example,1-indenyl and 2-indenyl.

Examples of the cycloalkyl-alkyl group include the groups in which oneor more hydrogen atoms of the alkyl group are substituted withcycloalkyl group(s), and include, for example, cyclopropylmethyl,1-cyclopropylethyl, 2-cyclopropylethyl, 3-cyclopropylpropyl,4-cyclopropylbutyl, 5-cyclopropylpentyl, 6-cyclopropylhexyl,cyclobutylmethyl, cyclopentylmethyl, cyclobutylmethyl,cyclopentylmethyl, cyclohexylmethyl, cyclohexylpropyl, cyclohexylbutyl,cycloheptylmethyl, cyclooctylmethyl, and 6-cyclooctylhexyl, which are C₄to C₁₄ cycloalkyl-alkyl groups.

Examples of the cycloalkylene group include, for example,cyclopropane-1,1-diyl, cyclopropane-1,2-diyl, cyclobutane-1,1-diyl,cyclobutane-1,2-diyl, cyclobutane-1,3-diyl, cyclopentane-1,1-diyl,cyclopentane-1,2-diyl, cyclopentane-1,3-diyl, cyclohexane-1,1-diyl,cyclohexane-1,2-diyl, cyclohexane-1,3-diyl, cyclohexane-1,4-diyl,cycloheptane-1,1-diyl, cycloheptane-1,2-diyl, cyclooctane-1,1,-diyl, andcyclooctane-1,2-diyl, which are C₃ to C₈ cycloalkylene groups.

Examples of the cycloalkenylene group include, for example,2-cyclopropene-1,1-diyl, 2-cyclobutene-1,1-diyl,2-cyclopentene-1,1-diyl, 3-cyclopentene-1,1-diyl,2-cyclohexene-1,1-diyl, 2-cyclohexene-1,2-diyl, 2-cyclohexene-1,4-diyl,3-cyclohexene-1,1-diyl, 1-cyclobutene-1,2-diyl, 1-cyclopentene-1,2-diyl,and 1-cyclohexene-1,2-diyl, which are C₃ to C₆ cycloalkenylene groups.

Examples of the aryl group include a monocyclic or a fused polycyclicaromatic hydrocarbon group, and include, for example, phenyl, 1-naphtyl,2-naphtyl, anthryl, phenanthryl, and acenaphthylenyl, which are C₆ toC₁₄ aryl groups. The aforementioned aryl group may be fused with theaforementioned C₃ to C₈ cycloalkyl group, C₃ to C₆ cycloalkenyl group,C₅ to C₆ cycloalkanedienyl group or the like, and examples include, forexample, 4-indanyl, 5-indanyl, 1,2,3,4-tetrahydronaphthalen-5-yl,1,2,3,4-tetrahydronaphthalen-6-yl, 3-acenaphthenyl, 4-acenaphthenyl,inden-4-yl, inden-5-yl, inden-6-yl, inden-7-yl, 4-phenalenyl,5-phenalenyl, 6-phenalenyl, 7-phenalenyl, 8-phenalenyl, and9-phenalenyl.

Examples of the arylene group include, for example, 1,2-phenylene,1,3-phenylene, 1,4-phenylene, naphthalene-1,2-diyl,naphthalene-1,3-diyl, naphthalene-1,4-diyl, naphthalene-1,5-diyl,naphthalene-1,6-diyl, naphthalene-1,7-diyl, naphthalene-1,8-diyl,naphthalene-2,3-diyl, naphthalene-2,4-diyl, naphthalene-2,5-diyl,naphthalene-2,6-diyl, naphthalene-2,7-diyl, naphthalene-2,8-diyl, andanthracene-1,4-diyl, which are C₆ to C₁₄ arylene groups.

Examples of the aralkyl group include the groups in which one or morehydrogen atoms of the alkyl group are substituted with aryl group(s),and include, for example, benzyl, 1-naphthylmethyl, 2-naphthylmethyl,anthracenylmethyl, phenanthrenylmethyl, acenaphthylenylmethyl,diphenylmethyl, 1-phenethyl, 2-phenethyl, 1-(1-naphthyl)ethyl,1-(2-naphthyl)ethyl, 2-(1-naphthyl)ethyl, 2-(2-naphthyl)ethyl,3-phenylpropyl, 3-(1-naphthyl)propyl, 3-(2-naphthyl)propyl,4-phenylbutyl, 4-(1-naphthyl)butyl, 4-(2-naphthyl)butyl, 5-phenylpentyl,5-(1-naphthyl)pentyl, 5-(2-naphthyl)pentyl, 6-phenylhexyl,6-(1-naphthyl)hexyl, and 6-(2-naphthyl)hexyl, which are C₇ to C₁₆aralkyl groups.

Examples of the bridged cyclic hydrocarbon group include, for example,bicyclo[2.1.0]pentyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.1]octyl, andadamantyl.

Examples of the spiro cyclic hydrocarbon group include, for example,spiro[3.4]octyl, and spiro[4.5]deca-1,6-dienyl.

Examples of the terpene hydrocarbon include, for example, geranyl,neryl, linalyl, phytyl, menthyl, and bornyl.

Examples of the halogenated alkyl group include the groups in which oneor more hydrogen atoms of the alkyl group are substituted with halogenatom(s), and include, for example, fluoromethyl, difluoromethyl,trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl,bromomethyl, dibromomethyl, tribromomethyl, iodomethyl, diiodomethyl,triiodomethyl, 2,2,2-trifluoroethyl, pentafluoroethyl,3,3,3-trifluoropropyl, heptafluoropropyl, heptafluoroisopropyl,nonafluorobutyl, and perfluorohexyl, which are C₁ to C₆ straight chainor branched chain halogenated alkyl groups substituted with 1 to 13halogen atoms.

Examples of the heterocyclic group include, for example, a monocyclic ora fused polycyclic hetero aryl group which comprises at least one heteroatom selected from oxygen atom, sulfur atom, nitrogen atom and the likeas ring-constituting atoms (ring forming atoms), and a monocyclic or afused polycyclic non-aromatic heterocyclic group which comprises atleast one hetero atom selected from oxygen atom, sulfur atom, nitrogenatom and the like as ring-constituting atoms (ring forming atoms). Whenthe heterocyclic group comprises two or more ring forming hetero atoms,each of them may be the same or different.

Examples of the monocyclic heteroaryl group include, for example,2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 1-pyrrolyl, 2-pyrrolyl,3-pyrrolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3-isoxazolyl,4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl,3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 1-imidazolyl,2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 1-pyrazolyl, 3-pyrazolyl,4-pyrazolyl, 5-pyrazolyl, (1,2,3-oxadiazol)-4-yl,(1,2,3-oxadiazol)-5-yl, (1,2,4-oxadiazol)-3-yl, (1,2,4-oxadiazol)-5-yl,(1,2,5-oxadiazol)-3-yl, (1,2,5-oxadiazol)-4-yl, (1,3,4-oxadiazol)-2-yl,(1,3,4-oxadiazol)-5-yl, furazanyl, (1,2,3-thiadiazol)-4-yl,(1,2,3-thiadiazol)-5-yl, (1,2,4-thiadiazol)-3-yl,(1,2,4-thiadiazol)-5-yl, (1,2,5-thiadiazol)-3-yl,(1,2,5-thiadiazol)-4-yl, (1,3,4-thiadiazolyl)-2-yl,(1,3,4-thiadiazolyl)-5-yl, (1H-1,2,3-triazol)-1-yl,(1H-1,2,3-triazol)-4-yl, (1H-1,2,3-triazol)-5-yl,(2H-1,2,3-triazol)-2-yl, (2H-1,2,3-triazol)-4-yl,(1H-1,2,4-triazol)-1-yl, (1H-1,2,4-triazol)-3-yl,(1H-1,2,4-triazol)-5-yl, (4H-1,2,4-triazol)-3-yl,(4H-1,2,4-triazol)-4-yl, (1H-tetrazol)-1-yl, (1H-tetrazol)-5-yl,(2H-tetrazol)-2-yl, (2H-tetrazol)-5-yl, 2-pyridyl, 3-pyridyl, 4-pyridyl,3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl,5-pyrimidinyl, 2-pyrazinyl, (1,2,3-triazin)-4-yl, (1,2,3-triazin)-5-yl,(1,2,4-triazin)-3-yl, (1,2,4-triazin)-5-yl, (1,2,4-triazin)-6-yl,(1,3,5-triazin)-2-yl, 1-azepinyl, 2-azepinyl, 3-azepinyl, 4-azepinyl,(1,4-oxazepin)-2-yl, (1,4-oxazepin)-3-yl, (1,4-oxazepin)-5-yl,(1,4-oxazepin)-6-yl, (1,4-oxazepin)-7-yl, (1,4-thiazepin)-2-yl,(1,4-thiazepin)-3-yl, (1,4-thiazepin)-5-yl, (1,4-thiazepin)-6-yl, and(1,4-thiazepin)-7-yl, which are 5 to 7-membered monocyclic heteroarylgroups.

Examples of the fused polycyclic heteroaryl group include, for example,2-benzofuranyl, 3-benzofuranyl, 4-benzofuranyl, 5-benzofuranyl,6-benzofuranyl, 7-benzofuranyl, 1-isobenzofuranyl, 4-isobenzofuranyl,5-isobenzofuranyl, 2-benzo[b]thienyl, 3-benzo[b]thienyl,4-benzo[b]thienyl, 5-benzo[b]thienyl, 6-benzo[b]thienyl,7-benzo[b]thienyl, 1-benzo[c]thienyl, 4-benzo[c]thienyl,5-benzo[c]thienyl, 1-indolyl, 1-indolyl, 2-indolyl, 3-indolyl,4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl, (2H-isoindol)-1-yl,(2H-isoindol)-2-yl, (2H-isoindol)-4-yl, (2H-isoindol)-5-yl,(1H-indazol)-1-yl, (1H-indazol)-3-yl, (1H-indazol)-4-yl,(1H-indazol)-5-yl, (1H-indazol)-6-yl, (1H-indazol)-7-yl,(2H-indazol)-1-yl, (2H-indazol)-2-yl, (2H-indazol)-4-yl,(2H-indazol)-5-yl, 2-benzoxazolyl, 2-benzoxazolyl, 4-benzoxazolyl,5-benzoxazolyl, 6-benzoxazolyl, 7-benzoxazolyl, (1,2-benzisoxazol)-3-yl,(1,2-benzisoxazol)-4-yl, (1,2-benzisoxazol)-5-yl,(1,2-benzisoxazol)-6-yl, (1,2-benzisoxazol)-7-yl,(2,1-benzisoxazol)-3-yl, (2,1-benzisoxazol)-4-yl,(2,1-benzisoxazol)-5-yl, (2,1-benzisoxazol)-6-yl,(2,1-benzisoxazol)-7-yl, 2-benzothiazolyl, 4-benzothiazolyl,5-benzothiazolyl, 6-benzothiazolyl, 7-benzothiazolyl,(1,2-benzisothiazol)-3-yl, (1,2-benzisothiazol)-4-yl,(1,2-benzisothiazol)-5-yl, (1,2-benzisothiazol)-6-yl,(1,2-benzisothiazol)-7-yl, (2,1-benzisothiazol)-3-yl,(2,1-benzisothiazol)-4-yl, (2,1-benzisothiazol)-5-yl,(2,1-benzisothiazol)-6-yl, (2,1-benzisothiazol)-7-yl,(1,2,3-benzoxadiazol)-4-yl, (1,2,3-benzoxadiazol)-5-yl,(1,2,3-benzoxadiazol)-6-yl, (1,2,3-benzoxadiazol)-7-yl,(2,1,3-benzoxadiazol)-4-yl, (2,1,3-benzoxadiazol)-5-yl,(1,2,3-benzothiadiazol)-4-yl, (1,2,3-benzothiadiazol)-5-yl,(1,2,3-benzothiadiazol)-6-yl, (1,2,3-benzothiadiazol)-7-yl,(2,1,3-benzothiadiazol)-4-yl, (2,1,3-benzothiadiazol)-5-yl,(1H-benzotriazol)-1-yl, (1H-benzotriazol)-4-yl, (1H-benzotriazol)-5-yl,(1H-benzotriazol)-6-yl, (1H-benzotriazol)-7-yl, (2H-benzotriazol)-2-yl,(2H-benzotriazol)-4-yl, (2H-benzotriazol)-5-yl, 2-quinolyl, 3-quinolyl,4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl,1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl,6-isoquinolyl, 7-isoquinolyl, 8-isoquinolyl, 3-cinnolinyl, 4-cinnolinyl,5-cinnolinyl, 6-cinnolinyl, 7-cinnolinyl, 8-cinnolinyl, 2-quinazolinyl,4-quinazolinyl, 5-quinazolinyl, 6-quinazolinyl, 7-quinazolinyl,8-quinazolinyl, 2-quinoxalinyl, 5-quinoxalinyl, 6-quinoxalinyl,1-phthalazinyl, 5-phthalazinyl, 6-phthalazinyl, 2-naphthyridinyl,3-naphthyridinyl, 4-naphthyridinyl, 2-purinyl, 6-purinyl, 7-purinyl,8-purinyl, 2-pteridinyl, 4-pteridinyl, 6-pteridinyl, 7-pteridinyl,1-carbazolyl, 2-carbazolyl, 3-carbazolyl, 4-carbazolyl, 9-carbazolyl,2-(α-carbolinyl), 3-(α-carbolinyl), 4-(α-carbolinyl), 5-(α-carbolinyl),6-(α-carbolinyl), 7-(α-carbolinyl), 8-(α-carbolinyl), 9-(α-carbolinyl),1-(β-carbolinyl), 3-(β-carbolinyl), 4-(β-carbolinyl), 5-(β-carbolinyl),6-(β-carbolinyl), 7-(β-carbolinyl), 8-(β-carbolinyl), 9-(β-carbolinyl),1-(γ-carbolinyl), 2-(γ-carbolinyl), 4-(γ-carbolinyl), 5-(γ-carbolinyl),6-(γ-carbolinyl), 7-(γ-carbolinyl), 8-(γ-carbolinyl), 9-(γ-carbolinyl),1-acridinyl, 2-acridinyl, 3-acridinyl, 4-acridinyl, 9-acridinyl,1-phenoxazinyl, 2-phenoxazinyl, 3-phenoxazinyl, 4-phenoxazinyl,10-phenoxazinyl, 1-phenothiazinyl, 2-phenothiazinyl, 3-phenothiazinyl,4-phenothiazinyl, 10-phenothiazinyl, 1-phenazinyl, 2-phenazinyl,1-phenanthridinyl, 2-phenanthridinyl, 3-phenanthridinyl,4-phenanthridinyl, 6-phenanthridinyl, 7-phenanthridinyl,8-phenanthridinyl, 9-phenanthridinyl, 10-phenanthridinyl,2-phenanthrolinyl, 3-phenanthrolinyl, 4-phenanthrolinyl,5-phenanthrolinyl, 6-phenanthrolinyl, 7-phenanthrolinyl,8-phenanthrolinyl, 9-phenanthrolinyl, 10-phenanthrolinyl,1-thianthrenyl, 2-thianthrenyl, 1-indolizinyl, 2-indolizinyl,3-indolizinyl, 5-indolizinyl, 6-indolizinyl, 7-indolizinyl,8-indolizinyl, 1-phenoxathiinyl, 2-phenoxathiinyl, 3-phenoxathiinyl,4-phenoxathiinyl, thieno[2,3,-b]furyl, pyrrolo[1,2-b]pyridazinyl,pyrazolo[1,5-a]pyridyl, imidazo[11,2-a]pyridyl, imidazo[1,5-a]pyridyl,imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrimidinyl,1,2,4-triazolo[4,3-a]pyridyl, and 1,2,4-triazolo[4,3-a]pyridazinyl,which are 8 to 14-membered fused polycyclic heteroaryl groups.

Examples of the monocyclic non-aromatic heterocyclic group include, forexample, 1-aziridinyl, 1-azetidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl,3-pyrrolidinyl, 2-tetrahydrofuryl, 3-tetrahydrofuryl, thiolanyl,1-imidazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 1-pyrazolidinyl,3-pyrazolidinyl, 4-pyrazolidinyl, 1-(2-pyrrolinyl), 1-(2-imidazolinyl),2-(2-imidazolinyl), 1-(2-pyrazolinyl), 3-(2-pyrazolinyl), piperidino,2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-homopiperidinyl,2-tetrahydropyranyl, morpholino, (thiomorpholin)-4-yl, 1-piperazinyl,and 1-homopiperazinyl, which are 3 to 7-membered saturated orunsaturated monocyclic non-aromatic heterocyclic groups.

Examples of the fused polycyclic non-aromatic heterocyclic groupinclude, for example, 2-quinuclidinyl, 2-chromanyl, 3-chromanyl,4-chromanyl, 5-chromanyl, 6-chromanyl, 7-chromanyl, 8-chromanyl,1-isochromanyl, 3-isochromanyl, 4-isochromanyl, 5-isochromanyl,6-isochromanyl, 7-isochromanyl, 8-isochromanyl, 2-thiochromanyl,3-thiochromanyl, 4-thiochromanyl, 5-thiochromanyl, 6-thiochromanyl,7-thiochromanyl, 8-thiochromanyl, 1-isothiochromanyl,3-isothiochromanyl, 4-isothiochromanyl, 5-isothiochromanyl,6-isothiochromanyl, 7-isothiochromanyl, 8-isothiochromanyl, 1-indolinyl,2-indolinyl, 3-indolinyl, 4-indolinyl, 5-indolinyl, 6-indolinyl,7-indolinyl, 1-isoindolinyl, 2-isoindolinyl, 4-isoindolinyl,5-isoindolinyl, 2-(4H-chromenyl), 3-(4H-chromenyl), 4-(4H-chromenyl),5-(4H-chromenyl), 6-(4H-chromenyl), 7-(4H-chromenyl), 8-(4H-chromenyl),1-isochromenyl, 3-isochromenyl, 4-isochromenyl, 5-isochromenyl,6-isochromenyl, 7-isochromenyl, 8-isochromenyl, 1-(1H-pyrrolidinyl),2-(1H-pyrrolidinyl), 3-(1H-pyrrolidinyl), 5-(1H-pyrrolidinyl),6-(1H-pyrrolidinyl), and 7-(1H-pyrrolidinyl), which are 8 to 10-memberedsaturated or unsaturated fused polycyclic non-aromatic heterocyclicgroups.

In the present specification, among the aforementioned heterocyclicgroups, a monocyclic or a fused polycyclic heteroaryl groups which mayhave one or more hetero atoms selected from oxygen atom, sulfur atom,nitrogen atom and the like as ring-constituting atoms (ring formingatoms) in addition to the nitrogen atom that has the bond, and amonocyclic or a fused polycyclic non-aromatic heterocyclic groups whichmay have one or more hetero atoms selected from oxygen atom, sulfuratom, nitrogen atom and the like as ring-constituting atoms (ringforming atoms) in addition to the nitrogen atom that has the bond, arereferred to as “cyclic amino group.” When the cyclic amino group has twoor more hetero atoms as ring-constituting atoms, each of them may be thesame or different. Examples include, for example, 1-pyrrolidinyl,1-imidazolidinyl, 1-pyrazolidinyl, 1-oxazolidinyl, 1-thiazolidinyl,piperidino, morpholino, 1-piperazinyl, thiomorpholin-4-yl,1-homopiperidinyl, 1-homopiperazinyl, 2-pyrolin-1-yl, 2-imidazolin-1-yl,2-pyrazolin-1-yl, 1-indolinyl, 2-isoindolinyl,1,2,3,4-tetrahydroquinolin-1-yl, 1,2,3,4-tetrahydroisoquinolin-2-yl,1-pyrrolyl, 1-imidazolyl, 1-pyrazolyl, 1-indolyl, 1-indazolyl, and2-isoindolyl.

In the present specification, the aforementioned cycloalkyl group,cycloalkenyl group, cycloalkanedienyl group, aryl group, andheterocyclic group are generically referred to as “cyclic group.”Furthermore, among said cyclic groups, particularly, aryl group,monocyclic heteroaryl group, and fused polycyclic heteroaryl group aregenerically referred to as “aromatic ring group.”

Examples of the hydrocarbon-oxy group include the groups in which ahydrogen atom of the hydroxy group is substituted with a hydrocarbongroup, and examples of the hydrocarbon include similar groups to theaforementioned hydrocarbon groups. Examples of the hydrocarbon-oxy groupinclude, for example, alkoxy group (alkyl-oxy group), alkenyl-oxy group,alkynyl-oxy group, cycloalkyl-oxy group, cycloalkyl-alkyl-oxy group andthe like, which are aliphatic hydrocarbon-oxy groups; aryl-oxy group;aralkyl-oxy group; and alkylene-dioxy group.

Examples of the alkoxy (alkyl-oxy group) include, for example, methoxy,ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy,tert-butoxy, n-pentyloxy, isopentyloxy, 2-methylbutoxy, 1-methylbutoxy,neopentyloxy, 1,2-dimethylpropoxy, 1-ethylpropoxy, n-hexyloxy,4-methylpentyloxy, 3-methylpentyloxy, 2-methylpentyloxy,1-methylpentyloxy, 3,3-dimethylbutoxy, 2,2-dimethybutoxy,1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy,2,3-dimethylbutoxy, 2-ethylbutoxy, 1-ethylbutoxy,1-ethyl-1-methylpropoxy, n-heptyloxy, n-octyloxy, n-nonyloxy,n-decyloxy, n-undecyloxy, n-dodecyloxy, n-tridecyloxy, n-tetradecyloxy,and n-pentadecyloxy, which are C₁ to C₁₅ straight chain or branchedchain alkoxy groups.

Examples of the alkenyl-oxy group include, for example, vinyloxy,(prop-1-en-1-yl)oxy, allyloxy, isopropenyloxy, (but-1-en-1-yl)oxy,(but-2-en-1-yl)oxy, (but-3-en-1-yl)oxy, (2-methylprop-2-en-1-yl)oxy,(1-methylprop-2-en-1-yl)oxy, (pent-1-en-1-yl)oxy, (pent-2-en-1-yl)oxy,(pent-3-en-1-yl)oxy, (pent-4-en-1-yl)oxy, (3-methylbut-2-en-1-yl)oxy,(3-methylbut-3-en-1-yl)oxy, (hex-1-en-1-yl)oxy, (hex-2-en-1-yl)oxy,(hex-3-en-1-yl)oxy, (hex-4-en-1-yl)oxy, (hex-5-en-1-yl)oxy,(4-methylpent-3-en-1-yl)oxy, (4-methylpent-3-en-1-yl)oxy,(hept-1-en-1-yl)oxy, (hept-6-en-1-yl)oxy, (oct-1-en-1-yl)oxy,(oct-7-en-1-yl)oxy, (non-1-en-1-yl)oxy, (non-8-en-1-yl)oxy,(dec-1-en-1-yl)oxy, (dec-9-en-1-yl)oxy, (undec-1-en-1-yl)oxy,(undec-10-en-1-yl)oxy, (dodec-1-en-1-yl)oxy, (dodec-11-en-1-yl)oxy,(tridec-1-en-1-yl)oxy, (tridec-12-en-1-yl)oxy, (tetradec-1-en-1-yl)oxy,(tetradec-13-en-1-yl)oxy, (pentadec-1-en-1-yl)oxy, and(pentadec-14-en-1-yl)oxy, which are C₂ to C₁₅ straight chain or branchedchain alkenyl-oxy groups.

Examples of the alkynyl-oxy group include, for example, ethynyloxy,(prop-1-yn-1-yl)oxy, (prop-2-yn-1-yl)oxy, (but-1-yn-1-yl)oxy,(but-3-yn-1-yl)oxy, (1-methylprop-2-yn-1-yl)oxy, (pent-1-yn-1-yl)oxy,(pent-4-yn-1-yl)oxy, (hex-1-yn-1-yl)oxy, (hex-5-yn-1-yl)oxy,(hept-1-yn-1-yl)oxy, (hept-6-yn-1-yl)oxy, (oct-1-yn-1-yl)oxy,(oct-7-yn-1-yl)oxy, (non-1-yn-1-yl)oxy, (non-8-yn-1-yl)oxy,(dec-1-yn-1-yl)oxy, (dec-9-yn-1-yl)oxy, (undec-1-yn-1-yl)oxy,(undec-10-yn-1-yl)oxy, (dodec-1-yn-1-yl)oxy, (dodec-11-yn-1-yl)oxy,(tridec-1-yn-1-yl)oxy, (tridec-12-yn-1-yl)oxy, (tetradec-1-yn-1-yl)oxy,(tetradec-13-yn-1-yl)oxy, (pentadec-1-yn-1-yl)oxy, and(pentadec-14-yn-1-yl)oxy, which are C₂ to C₁₅ straight chain or branchedchain alkynyl-oxy groups.

Examples of the cycloalkyl-oxy group include, for example, cyclopropoxy,cyclobutoxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, andcyclooctyloxy, which are C₃ to C₈ cycloalkyl-oxy groups.

Examples of the cycloalkyl-alkyl-oxy group include, for example,cyclopropylmethoxy, 1-cyclopropylethoxy, 2-cyclopropylethoxy,3-cyclopropylpropoxy, 4-cyclopropylbutoxy, 5-cyclopropylpentyloxy,6-cyclopropylhexyloxy, cyclobutylmethoxy, cyclopentylmethoxy,cyclobutylmethoxy, cyclopentylmethoxy, cyclohexylmethoxy,2-cyclohexylethoxy, 3-cyclohexylpropoxy, 4-cyclohexylbutoxy,cycloheptylmethoxy, cyclooctylmethoxy, and 6-cyclooctylhexyloxy, whichare C₄ to C₁₄ cycloalkyl-alkyl-oxy groups.

Examples of the aryl-oxy group include, for example, phenoxy,1-naphthyloxy, 2-naphthyloxy, anthryloxy, phenanthryloxy, andacenaphthylenyloxy, which are C₆ to C₁₄ aryl-oxy groups.

Examples of the aralkyl-oxy group include, for example, benzyloxy,1-naphthylmethoxy, 2-naphthylmethoxy, anthracenylmethoxy,phenanthrenylmethoxy, acenaphthylenylmethoxy, diphenylmethoxy,1-phenethyloxy, 2-phenethyloxy, 1-(1-naphthyl)ethoxy,1-(2-naphthyl)ethoxy, 2-(1-naphthyl)ethoxy, 2-(2-naphthyl)ethoxy,3-phenylpropoxy, 3-(1-naphthyl)propoxy, 3-(2-naphthyl)propoxy,4-phenylbutoxy, 4-(1-naphthyl)butoxy, 4-(2-naphthyl)butoxy,5-phenylpentyloxy, 5-(1-naphthyl)pentyloxy, 5-(2-naphthyl)pentyloxy,6-phenylhexyloxy, 6-(1-naphthyl)hexyloxy, and 6-(2-naphthyl)hexyloxy,which are C₇ to C₁₆ aralkyl-oxy groups.

Examples of the alkylenedioxy group include, for example,methylenedioxy, ethylenedioxy, 1-methylmethylenedioxy, and1,1-dimethylmethylenedioxy.

Examples of the halogenated alkoxy group (halogenated alkyl-oxy group)include the groups in which a hydrogen atom of the hydroxy group issubstituted with a halogenated alkyl group, and include, for example,fluoromethoxy, difluoromethoxy, chloromethoxy, bromomethoxy,iodomethoxy, trifluoromethoxy, trichloromethoxy, 2,2,2-trifluoroethoxy,pentafluoroethoxy, 3,3,3-trifluoropropoxy, heptafluoropropoxy,heptafluoroisopropoxy, nonafluorobutoxy, and perfluorohexyloxy, whichare C₁ to C₆ straight chain or branched chain halogenated alkoxy groupssubstituted with 1 to 13 halogen atoms.

Examples of the heterocyclic-oxy group include the groups in which ahydrogen atom of the hydroxy group is substituted with a heterocyclicgroup, and examples of the heterocyclic ring include similar groups tothe aforementioned heterocyclic groups. Examples of the heterocyclic-oxygroup include, for example, a monocyclic heteroaryl-oxy group, a fusedpolycyclic heteroaryl-oxy group, a monocyclic non-aromaticheterocyclic-oxy group, and a fused polycyclic non-aromaticheterocyclic-oxy group.

Examples of the monocyclic heteroaryl-oxy group include, for example,3-thienyloxy, (isoxazol-3-yl)oxy, (thiazol-4-yl)oxy, 2-pyridyloxy,3-pyridyloxy, 4-pyridyloxy, and (pyrimidin-4-yl)oxy.

Examples of the fused polycyclic heteroaryl-oxy group include, forexample, 5-indolyloxy, (benzimidazol-2-yl)oxy, 2-quinolyloxy,3-quinolyloxy, and 4-quinolyloxy.

Examples of the monocyclic non-aromatic heterocyclic-oxy group include,for example, 3-pyrrolidinyloxy, and 4-piperidinyloxy.

Examples of the fused polycyclic non-aromatic heterocyclic-oxy groupinclude, for example, 3-indolynyloxy, and 4-chromanyloxy.

Examples of the hydrocarbon-sulfanyl group include the groups in which ahydrogen atom of the sulfanyl group is substituted with a hydrocarbongroup, and examples of the hydrocarbon include similar groups to theaforementioned hydrocarbon groups. Examples of the hydrocarbon-sulfanylgroups include, for example, alkyl-sulfanyl group, alkenyl-sulfanylgroup, alkynyl-sulfanyl group, cycloalkyl-sulfanyl group,cycloalkyl-alkyl-sulfanyl group and the like, which are aliphatichydrocarbon-sulfanyl groups; aryl-sulfanyl group, and aralkyl-sulfanylgroup.

Examples of the alkyl-sulfanyl group include, for example,methylsulfanyl, ethylsulfanyl, n-propylsulfanyl, isopropylsulfanyl,n-butylsulfanyl, isobutylsulfanyl, sec-butylsulfanyl,tert-butylsulfanyl, n-pentylsulfanyl, isopentylsulfanyl,(2-methylbutyl)sulfanyl, (1-methylbutyl)sulfanyl, neopentylsulfanyl,(1,2-dimethylpropyl)sulfanyl, (1-ethylpropyl)sulfanyl, n-hexylsulfanyl,(4-methylpentyl)sulfanyl, (3-methylpentyl)sulfanyl,(2-methylpentyl)sulfanyl, (1-methylpentyl)sulfanyl,(3,3-dimethylbutyl)sulfanyl, (2,2-dimethylbutyl)sulfanyl,(1,1-dimethylbutyl)sulfanyl, (1,2-dimethylbutyl)sulfanyl,(1,3-dimethylbutyl)sulfanyl, (2,3-dimethylbutyl)sulfanyl,(2-ethylbutyl)sulfanyl, (1-ethylbutyl)sulfanyl,(1-ethyl-1-methylpropyl)sulfanyl, n-heptylsulfanyl, n-octylsulfanyl,n-nonylsulfanyl, n-decylsulfanyl, n-undecylsulfanyl, n-dodecylsulfanyl,n-tridecylsulfanyl, n-tetradecylsulfanyl, and n-pentadecylsulfanyl,which are C₁ to C₁₅ straight chain or branched chain alkyl-sulfanylgroups.

Examples of the alkenyl-sulfanyl group include, for example,vinylsulfanyl, (prop-1-en-1-yl)sulfanyl, allylsulfanyl,isopropenylsulfanyl, (but-1-en-1-yl)sulfanyl, (but-2-en-1-yl)sulfanyl,(but-3-en-1-yl)sulfanyl, (2-methylprop-2-en-1-yl)sulfanyl,(1-methylprop-2-en-1-yl)sulfanyl, (pent-1-en-1-yl)sulfanyl,(pent-2-en-1-yl)sulfanyl, (pent-3-en-1-yl)sulfanyl,(pent-4-en-1-yl)sulfanyl, (3-methylbut-2-en-1-yl)sulfanyl,(3-methylbut-3-en-1-yl)sulfanyl, (hex-1-en-1-yl)sulfanyl,(hex-2-en-1-yl)sulfanyl, (hex-3-en-1-yl)sulfanyl,(hex-4-en-1-yl)sulfanyl, (hex-5-en-1-yl)sulfanyl,(4-methylpent-3-en-1-yl)sulfanyl, (4-methylpent-3-en-1-yl)sulfanyl,(hept-1-en-1-yl)sulfanyl, (hept-6-en-1-yl)sulfanyl,(oct-1-en-1-yl)sulfanyl, (oct-7-en-1-yl)sulfanyl,(non-1-en-1-yl)sulfanyl, (non-8-en-1-yl)sulfanyl,(dec-1-en-1-yl)sulfanyl, (dec-9-en-1-yl)sulfanyl,(undec-1-en-1-yl)sulfanyl, (undec-10-en-1-yl)sulfanyl,(dodec-1-en-1-yl)sulfanyl, (dodec-11-en-1-yl)sulfanyl,(tridec-1-en-1-yl)sulfanyl, (tridec-12-en-1-yl)sulfanyl,(tetradec-1-en-1-yl)sulfanyl, (tetradec-13-en-1-yl)sulfanyl,(pentadec-1-en-1-yl)sulfanyl, and (pentadec-14-en-1-yl)sulfanyl, whichare C₂ to C₁₅ straight chain or branched chain alkenyl-sulfanyl groups.

Examples of the alkynyl-sulfanyl group include, for example,ethynylsulfanyl, (prop-1-yn-1-yl)sulfanyl, (prop-2-yn-1-yl)sulfanyl,(but-1-yn-1-yl)sulfanyl, (but-3-yn-1-yl)sulfanyl,(1-methylprop-2-yn-1-yl)sulfanyl, (pent-1-yn-1-yl)sulfanyl,(pent-4-yn-1-yl)sulfanyl, (hex-1-yn-1-yl)sulfanyl,(hex-5-yn-1-yl)sulfanyl, (hept-1-yn-1-yl)sulfanyl,(hept-6-yn-1-yl)sulfanyl, (oct-1-yn-1-yl)sulfanyl,(oct-7-yn-1-yl)sulfanyl, (non-1-yn-1-yl)sulfanyl,(non-8-yn-1-yl)sulfanyl, (dec-1-yn-1-yl)sulfanyl,(dec-9-yn-1-yl)sulfanyl, (undec-1-yn-1-yl)sulfanyl,(undec-10-yn-1-yl)sulfanyl, (dodec-1-yn-1-yl)sulfanyl,(dodec-11-yn-1-yl)sulfanyl, (tridec-1-yn-1-yl)sulfanyl,(tridec-12-yn-1-yl)sulfanyl, (tetradec-1-yn-1-yl)sulfanyl,(tetradec-13-yn-1-yl)sulfanyl, (pentadec-1-yn-1-yl)sulfanyl, and(pentadec-14-yn-1-yl)sulfanyl, which are C₂ to C₁₅ straight chain orbranched chain alkynyl-sulfanyl groups.

Examples of the cycloalkyl-sulfanyl group include, for example,cyclopropylsulfanyl, cyclobutylsulfanyl, cyclopentylsulfanyl,cyclohexylsulfanyl, cycloheptylsulfanyl, and cyclooctylsulfanyl, whichare C₃ to C₈ cycloalkyl-sulfanyl groups.

Examples of the cycloalkyl-alkyl-sulfanyl group include, for example,(cyclopropylmethyl)sulfanyl, (1-cyclopropylethyl)sulfanyl,(2-cyclopropylethyl)sulfanyl, (3-cyclopropylpropyl)sulfanyl,(4-cyclopropylbutyl)sulfanyl, (5-cyclopropylpentyl)sulfanyl,(6-cyclopropylhexyl)sulfanyl, (cyclobutylmethyl)sulfanyl,(cyclopentylmethyl)sulfanyl, (cyclobutylmethyl)sulfanyl,(cyclopentylmethyl)sulfanyl, (cyclohexylmethyl)sulfanyl,(2-cyclohexylethyl)sulfanyl, (3-cyclohexylpropyl)sulfanyl,(4-cyclohexylbutyl)sulfanyl, (cycloheptylmethyl)sulfanyl,(cyclooctylmethyl)sulfanyl, and (6-cyclooctylhexyl)sulfanyl, which areC₄ to C₁₄ cycloalkyl-alkyl-sulfanyl groups.

Examples of the aryl-sulfanyl group include, for example,phenylsulfanyl, 1-naphthylsulfanyl, 2-naphthylsulfanyl, anthrylsulfanyl,fenanthrylsulfanyl, and acenaphthylenylsulfanyl, which are C₆ to C₁₄aryl-sulfanyl groups.

Examples of the aralkyl-sulfanyl group include, for example,benzylsulfanyl, (1-naphthylmethyl)sulfanyl, (2-naphthylmethyl)sulfanyl,(anthracenylmethyl)sulfanyl, (phenanthrenylmethyl)sulfanyl,(acenaphthylenylmethyl)sulfanyl, (diphenylmethyl)sulfanyl,(1-phenethyl)sulfanyl, (2-phenethyl)sulfanyl,(1-(1-naphthyl)ethyl)sulfanyl, (1-(2-naphthyl)ethyl)sulfanyl,(2-(1-naphthyl)ethyl)sulfanyl, (2-(2-naphthyl)ethyl)sulfanyl,(3-phenylpropyl)sulfanyl, (3-(1-naphthyl)propyl)sulfanyl,(3-(2-naphthyl)propyl)sulfanyl, (4-phenylbutyl)sulfanyl,(4-(1-naphthyl)butyl)sulfanyl, (4-(2-naphthyl)butyl)sulfanyl,(5-phenylpentyl)sulfanyl, (5-(1-naphthyl)pentyl)sulfanyl,(5-(2-naphthyl)pentyl)sulfanyl, (6-phenylhexyl)sulfanyl,(6-(1-naphthyl)hexyl)sulfanyl, and (6-(2-naphthyl)hexyl)sulfanyl, whichare C₇ to C₁₆ aralkyl-sulfanyl groups.

Examples of the halogenated alkyl-sulfanyl group include the groups inwhich a hydrogen atom of the sulfanyl group is substituted with ahalogenated alkyl group, and include, for example,(fluoromethyl)sulfanyl, (chloromethyl)sulfanyl, (bromomethyl)sulfanyl,(iodomethyl)sulfanyl, (difluoromethyl)sulfanyl,(trifluoromethyl)sulfanyl, (trichloromethyl)sulfanyl,(2,2,2-trifluoroethyl)sulfanyl, (pentafluoroethyl)sulfanyl,(3,3,3-trifluoropropyl)sulfanyl, (heptafluoropropyl)sulfanyl,(heptafluoroisopropyl)sulfanyl, (nonafluorobutyl)sulfanyl, and(perfluorohexyl)sulfanyl, which are C₁ to C₆ straight chain or branchedchain halogenated alkyl-sulfanyl groups substituted with 1 to 13 halogenatoms.

Examples of the heterocyclic-sulfanyl group include the groups in whicha hydrogen atom of the sulfanyl group is substituted with a heterocyclicgroup, and examples of the heterocyclic ring include similar groups tothe aforementioned heterocyclic groups. Examples of theheterocyclic-sulfanyl group include, for example, a monocyclicheteroaryl-sulfanyl group, a fused polycyclic heteroaryl-sulfanyl group,a monocyclic non-aromatic heterocyclic-sulfanyl group, and a fusedpolycyclic non-aromatic heterocyclic-sulfanyl group.

Examples of the monocyclic heteroaryl-sulfanyl group include, forexample, (imidazol-2-yl)sulfanyl, (1,2,4-triazol-2-yl)sulfanyl,(pyridin-2-yl)sulfanyl, (pyridin-4-yl)sulfanyl, and(pyrimidin-2-yl)sulfanyl.

Examples of the fused polycyclic heteroaryl-sulfanyl group include, forexample, (benzimidazol-2-yl)sulfanyl, (quinolin-2-yl)sulfanyl, and(quinolin-4-yl)sulfanyl.

Examples of the monocyclic non-aromatic heterocyclic-sulfanyl groupsinclude, for example, (3-pyrrolidinyl)sulfanyl, and(4-piperidinyl)sulfanyl.

Examples of the fused polycyclic non-aromatic heterocyclic-sulfanylgroup include, for example, (3-indolinyl)sulfanyl, and(4-chromanyl)sulfanyl.

Examples of the acyl group include, for example, formyl group,glyoxyloyl group, thioformyl group, and groups represented by thefollowing formulas:

wherein each of R^(a1) and R^(b1) independently represents a hydrocarbongroup or a heterocyclic group, or when each of R^(a1) and R^(b1) bindsto the same nitrogen atom, R^(a1) and R^(b1) may combine to each other,together with the nitrogen atom to which they bind, to form a cyclicamino group.

In the definition of the aforementioned acyl group, among the groupsrepresented by the formula (ω-1A), those groups in which R^(a1) is ahydrocarbon group are referred to as “hydrocarbon-carbonyl group” whoseexamples include, for example, acetyl, propionyl, butyryl, isobutyryl,valeryl, isovaleryl, pivaloyl, lauroyl, myristoryl, palmitoyl, acryloyl,propioloyl, methacryloyl, crotonoyl, isocrotonoyl, cyclohexylcarbonyl,cyclohexylmethylcarbonyl, benzoyl, 1-naphthoyl, 2-naphthoyl, andphenylacetyl, and those groups in which R^(a1) is a heterocyclic groupare referred to as “heterocyclic ring-carbonyl group” whose examplesinclude, for example, 2-thenoyl, 3-furoyl, nicotinoyl, andisonicotinoyl.

Among the groups represented by the formula (ω-2A), those groups inwhich R^(a1) is a hydrocarbon group are referred to as“hydrocarbon-oxy-carbonyl group” whose examples include, for example,methoxycarbonyl, ethoxycarbonyl, phenoxycarbonyl, and benzyloxycarbonyl,and those groups in which R^(a1) is a heterocyclic group are referred toas “heterocyclic ring-oxy-carbonyl group” whose examples include, forexample, 3-pyridyloxycarbonyl.

Among the groups represented by the formula (ω-3A), those groups inwhich R^(a1) is a hydrocarbon group are referred to as“hydrocarbon-carbonyl-carbonyl group” whose examples include, forexample, pyruvoyl, and those groups in which R^(a1) is a heterocyclicgroup are referred to as “heterocyclic ring-carbonyl-carbonyl group.”

Among the groups represented by the formula (ω-4A), those groups inwhich R^(a1) is a hydrocarbon group are referred to as“hydrocarbon-oxy-carbonyl-carbonyl group” whose examples include, forexample, methoxalyl and ethoxalyl groups, and those groups in whichR^(a1) is a heterocyclic group are referred to as “heterocyclicring-oxy-carbonyl-carbonyl group.”

Among the groups represented by the formula (ω-5A), those groups inwhich R^(a1) is a hydrocarbon group are referred to as“hydrocarbon-sulfanyl-carbonyl group,” and those groups in which R^(a1)is a heterocyclic group are referred to as “heterocyclicring-sulfanyl-carbonyl group.”

Among the groups represented by the formula (ω-6A), those groups inwhich R^(a1) is a hydrocarbon group are referred to as“hydrocarbon-thiocarbonyl group,” and those groups in which R^(a1) is aheterocyclic group are referred to as “heterocyclic ring-thiocarbonylgroup.”

Among the groups represented by the formula (ω-7A), those groups inwhich R^(a1) is a hydrocarbon group are referred to as“hydrocarbon-oxy-thiocarbonyl group,” and those groups in which R^(a1)is a heterocyclic group are referred to as “heterocyclicring-oxy-thiocarbonyl group.”

Among the groups represented by the formula (ω-8A), those groups inwhich R^(a1) is a hydrocarbon group are referred to as“hydrocarbon-sulfanyl-thiocarbonyl group,” and those groups in whichR^(a1) is a heterocyclic group are referred to as “heterocyclicring-sulfanyl-thiocarbonyl group.”

Among the groups represented by the formula (ω-9A), those groups inwhich R^(a1) is a hydrocarbon group are referred to as referred to as“N-hydrocarbon-carbamoyl group” whose examples include, for example,N-methylcarbamoyl group, and those groups in which R^(a1) is aheterocyclic group are referred to as “N-heterocyclic ring-carbamoylgroup.”

Among the groups represented by the formula (ω-10A), those groups inwhich both R^(a1) and R^(b1) are hydrocarbon groups are referred to as“N,N-di(hydrocarbon)-carbamoyl group” whose examples include, forexample, N,N-dimethylcarbamoyl group, those groups in which both R^(a1)and R^(b1) are heterocyclic groups are referred to as“N,N-di(heterocyclic ring)-carbamoyl group,” those groups in whichR^(a1) is a hydrocarbon group and R^(b1) is a heterocyclic group arereferred to as “N-hydrocarbon-N-heterocyclic ring-substituted carbamoylgroup,” and those groups in which R^(a1) and R^(b1) combine to eachother, together with the nitrogen atom to which they bind, to form acyclic amino group are referred to as “cyclic amino-carbonyl group”whose examples include, for example, morpholino-carbonyl.

Among the groups represented by the formula (ω-11A), those groups inwhich R^(a1) is a hydrocarbon group are referred to as“N-hydrocarbon-thiocarbamoyl group,” and those groups in which R^(a1) isa heterocyclic group are referred to as “N-heterocyclicring-thiocarbamoyl group.”

Among the groups represented by the formula (ω-12A), those groups inwhich both R^(a1) and R^(b1) are hydrocarbon groups are referred to as“N,N-di(hydrocarbon)-thiocarbamoyl group,” those groups in which bothR^(a1) and R^(b1) are heterocyclic groups are referred to as“N,N-di(heterocyclic ring)-thiocarbamoyl group,” those groups in whichR^(a1) is a hydrocarbon group and R^(b1) is a heterocyclic group arereferred to as “N-hydrocarbon-N-heterocyclic ring-thiocarbamoyl group,”and those groups in which R^(a1) and R^(b1) combine to each other,together with the nitrogen atom to which they bind, to form a cyclicamino group are referred to as “cyclic amino-thiocarbonyl group.”

Among the groups represented by the formula (ω-13A), those groups inwhich R^(a1) is a hydrocarbon group are referred to as“N-hydrocarbon-sulfamoyl group,” and those groups in which R^(a1) is aheterocyclic group are referred to as “N-heterocyclic ring-sulfamoylgroup.”

Among the groups represented by the formula (ω-14A), those groups inwhich both R^(a1) and R^(b1) are hydrocarbon groups are referred to as“N,N-di(hydrocarbon)-sulfamoyl group” whose examples include, forexample, N,N-dimethylsulfamoyl group, those groups in which both R^(a1)and R^(b1) are heterocyclic groups are referred to as“N,N-di(heterocyclic ring)-sulfamoyl group,” those groups in whichR^(a1) is a hydrocarbon group and R^(b1) is a heterocyclic group arereferred to as “N-hydrocarbon-N-heterocyclic ring-sulfamoyl group,” andthose groups in which R^(a1) and R^(b1) combine to each other, togetherwith the nitrogen atom to which they bind, to form a cyclic amino groupare referred to as “cyclic amino-sulfonyl group” whose examples include,for example 1-pyrrolylsulfonyl.

Among the groups represented by the formula (ω-15A), those groups inwhich R^(a1) is a hydrocarbon group are referred to as“N-hydrocarbon-sulfinamoyl group,” and those groups in which R^(a1) is aheterocyclic group are referred to as “N-heterocyclic ring-sulfinamoylgroup.”

Among the groups represented by the formula (ω-16A), those groups inwhich both R^(a1) and R^(b1) are hydrocarbon groups are referred to as“N,N-di(hydrocarbon)-sulfinamoyl group,” those groups in which bothR^(a1) and R^(b1) are heterocyclic groups are referred to as“N,N-di(heterocyclic ring)-sulfinamoyl group,” those groups in whichR^(a1) is a hydrocarbon group and R^(b1) is a heterocyclic group arereferred to as “N-hydrocarbon-N-heterocyclic ring-sulfinamoyl group,”and those groups in which R^(a1) and R^(b1) combine to each other,together with the nitrogen atom to which they bind, to form a cyclicamino group are referred to as “cyclic amino-sulfinyl group.”

Among the groups represented by the formula (ω-17A), those groups inwhich R^(a1) is a hydrocarbon group are referred to as“hydrocarbon-oxy-sulfonyl group,” and those groups in which R^(a1) is aheterocyclic group are referred to as “heterocyclic ring-oxy-sulfonylgroup.”

Among the groups represented by the formula (ω-18A), those groups inwhich R^(a1) is a hydrocarbon group are referred to as“hydrocarbon-oxy-sulfinyl group,” and those groups in which R^(a1) is aheterocyclic group are referred to as “heterocyclic ring-oxy-sulfinylgroup.”

Among the groups represented by the formula (ω-19A), those groups inwhich both R^(a1) and R^(b1) are hydrocarbon groups are referred to as“O,O′-di(hydrocarbon)-phosphono group,” those groups in which bothR^(a1) and R^(b1) are heterocyclic groups are referred to as“O,O′-di(heterocyclic ring)-phosphono group,” and those groups in whichR^(a1) is a hydrocarbon group and R^(b1) is a heterocyclic group arereferred to as “O-hydrocarbon-O′-heterocyclic ring-phosphono group.”

Among the groups represented by the formula (ω-20A), those groups inwhich R^(a1) is a hydrocarbon group are referred to as“hydrocarbon-sulfonyl group” whose examples include, for example,methanesulfonyl and benzenesulfonyl, and those groups in which R^(a1) isa heterocyclic group are referred to as “heterocyclic ring-sulfonylgroup.”

Among the groups represented by the formula (ω-21A), those groups inwhich R^(a1) is a hydrocarbon group are referred to as“hydrocarbon-sulfinyl group” whose examples include, for example,methylsulfinyl and benzenesulfinyl, and those groups in which R^(a1) isa heterocyclic group are referred to as “heterocyclic ring-sulfinylgroup.”

Examples of the hydrocarbon in the groups represented by theaforementioned formulas (ω-1A) through (ω-21A) include the similargroups to the aforementioned hydrocarbon group. Examples of thehydrocarbon-carbonyl group represented by the formula (ω-1A) include,for example, an alkyl-carbonyl group, an alkenyl-carbonyl group, analkynyl-carbonyl group, a cycloalkyl-carbonyl group, acycloalkenyl-carbonyl group, a cycloalkanedienyl-carbonyl group, acycloalkyl-alkyl-carbonyl group, which are aliphatichydrocarbon-carbonyl groups; an aryl-carbonyl group; an aralkyl-carbonylgroup; a bridged cyclic hydrocarbon-carbonyl group; a spirocyclichydrocarbon-carbonyl group; and a terpene family hydrocarbon-carbonylgroup. In the following descriptions, groups represented by the formulas(ω-2A) through (ω-21A) are similar to those explained above.

Examples of the heterocyclic ring in the groups represented by theaforementioned formulas (ω-1A) through (ω-21A) include similar groups tothe aforementioned heterocyclic group. Examples of the heterocyclicring-carbonyl group represented by the formula (ω-1A) include, forexample, a monocyclic heteroaryl-carbonyl group, a fused polycyclicheteroaryl-carbonyl group, a monocyclic non-aromatic heterocyclicring-carbonyl group, and a fused polycyclic non-aromatic heterocyclicring-carbonyl group. In the following descriptions, groups representedby the formulas (ω-2A) through (ω-21A) are similar to those explainedabove.

Examples of the cyclic amino in the groups represented by theaforementioned formulas (ω-10A) through (ω-16A) include similar groupsto the aforementioned cyclic amino group.

In the present specification, when a certain functional group is definedas “which may be substituted,” the definition means that the functionalgroup may sometimes have one or more substituents at chemicallysubstitutable positions, unless otherwise specifically mentioned. Kindof substituents, number of substituents, and the position ofsubstituents existing in the functional groups are not particularlylimited, and when two or more substituents exist, they may be the sameor different. Examples of the substituent existing in the functionalgroup include, for example, halogen atoms, oxo group, thioxo group,nitro group, nitroso group, cyano group, isocyano group, cyanato group,thiocyanato group, isocyanato group, isothiocyanato group, hydroxygroup, sulfanyl group, carboxy group, sulfanylcarbonyl group, oxalogroup, methooxalo group, thiocarboxy group, dithiocarboxy group,carbamoyl group, thiocarbamoyl group, sulfo group, sulfamoyl group,sulfino group, sulfinamoyl group, sulfeno group, sulfenamoyl group,phosphono group, hydroxyphosphonyl group, hydrocarbon group,heterocyclic group, hydrocarbon-oxy group, heterocyclic ring-oxy group,hydrocarbon-sulfanyl group, heterocyclic ring-sulfanyl group, acylgroup, amino group, hydrazino group, hydrazono group, diazenyl group,ureido group, thioureido group, guanidino group, carbamoimidoyl group(amidino group), azido group, imino group, hydroxyamino group,hydroxyimino group, aminooxy group, diazo group, semicarbazino group,semicarbazono group, allophanyl group, hydantoyl group, phosphano group,phosphoroso group, phospho group, boryl group, silyl group, stannylgroup, selanyl group, oxido group and the like.

When two or more substituents exist according to the aforementioneddefinition of “which may be substituted,” said two or more substituentsmay combine to each other, together with atom(s) to which they bind, toform a ring. One or more substituents may exist on said ring. The ringmay be monocyclic or fused polycyclic, and aromatic or non-aromatic.

The above substituents according to the aforementioned definition of“which may be substituted” may further be substituted with theaforementioned substituents at the chemically substitutable positions onthe substituent. Kind of substituents, number of substituents, andpositions of substituents are not particularly limited, and when thesubstituents are substituted with two or more substituents, they may bethe same or different. Examples of the substituent include, for example,a halogenated alkyl-carbonyl group whose examples include, for example,trifluoroacetyl, a halogenated alkyl-sulfonyl group whose examplesinclude, for example, trifluoromethanesulfonyl, an acyl-oxy group, anacyl-sulfanyl group, an N-hydrocarbon-amino group, anN,N-di(hydrocarbon)-amino group, an N-heterocyclic ring-amino group, anN-hydrocarbon-N-heterocyclic ring-amino group, an acyl-amino group, anda di(acyl)-amino group. Moreover, one or more arbitrary substituents mayfurther exist on the aforementioned substituent.

Examples of the acyl-oxy group include the groups in which hydrogen atomof hydroxy group is substituted with acyl group, and include, forexample, formyloxy group, glyoxyloyloxy group, thioformyloxy group, andgroups represented by the following formulas:

wherein each of R^(a2) and R^(b2) independently represents a hydrocarbongroup or a heterocyclic group, or when each of R^(b2) and R^(b2) bindsto the same nitrogen atom, R^(a2) and R^(b2) may combine to each other,together with the nitrogen atom to which they bind, to form a cyclicamino group.

In the definition of the aforementioned acyl-oxy group, among the groupsrepresented by the formula (ω-1B), those groups in which R^(a2) is ahydrocarbon group are referred to as “hydrocarbon-carbonyl-oxy group”whose examples include, for example, acetoxy and benzoyloxy, and thosegroups in which R^(a2) is a heterocyclic group are referred to as“heterocyclic ring-carbonyl-oxy group.”

Among the groups represented by the formula (ω-2B), those groups inwhich R^(a2) is a hydrocarbon group are referred to as“hydrocarbon-oxy-carbonyl-oxy group,” and those groups in which R^(a2)is a heterocyclic group are referred to as “heterocyclicring-oxy-carbonyl-oxy group.”

Among the groups represented by the formula (ω-3B), those groups inwhich R^(a2) is a hydrocarbon group are referred to as“hydrocarbon-carbonyl-carbonyl-oxy group,” and those groups in whichR^(a2) is a heterocyclic group are referred to as “heterocyclicring-carbonyl-carbonyl-oxy group.”

Among the groups represented by the formula (ω-4B), those groups inwhich R^(a2) is a hydrocarbon group are referred to as“hydrocarbon-oxy-carbonyl-carbonyl-oxy group,” and those groups in whichR^(a2) is a heterocyclic group are referred to as “heterocyclicring-oxy-carbonyl-carbonyl-oxy group.”

Among the groups represented by the formula (ω-5B), those groups inwhich R^(a2) is a hydrocarbon group are referred to as“hydrocarbon-sulfanyl-carbonyl-oxy group,” and those groups where R^(a2)is a heterocyclic group are referred to as “heterocyclicring-sulfanyl-carbonyl-oxy group.”

Among the groups represented by the formula (ω-6B), those groups inwhich R^(a2) is a hydrocarbon group are referred to as“hydrocarbon-thiocarbonyl-oxy group,” and those groups where R^(a2) is aheterocyclic group are referred to as “heterocyclicring-thiocarbonyl-oxy group.”

Among the groups represented by the formula (ω-7B), those groups inwhich R^(a2) is a hydrocarbon group are referred to as“hydrocarbon-oxy-thiocarbonyl-oxy group,” and those groups in whichR^(a2) is a heterocyclic group are referred to as “heterocyclicring-oxy-thiocarbonyl-oxy group.”

Among the groups represented by the formula (ω-8B), those groups inwhich R^(a2) is a hydrocarbon group are referred to as“hydrocarbon-sulfanyl-thiocarbonyl-oxy group,” and those groups whereinR^(a2) is a heterocyclic group are referred to as “heterocyclicring-sulfanyl-thiocarbonyl-oxy group.”

Among the groups represented by the formula (ω-9B), those groups inwhich R^(a2) is a hydrocarbon group are referred to as“N-hydrocarbon-carbamoyl-oxy group,” and those groups in which R^(a2) isa heterocyclic group are referred to as “N-heterocyclicring-carbamoyl-oxy group.”

Among the groups represented by the formula (ω-10B), those groups inwhich both R^(a2) and R^(b2) are hydrocarbon groups are referred to as“N,N-di(hydrocarbon)-carbamoyl-oxy group,” those groups in which bothR^(a2) and R^(b2) are heterocyclic groups are referred to as“N,N-di(heterocyclic ring)-carbamoyl-oxy group,” those groups in whichR^(a2) is a hydrocarbon group and R^(b2) is a heterocyclic group arereferred to as “N-hydrocarbon-N-heterocyclic ring-carbamoyl-oxy group,”and those groups in which R^(a2) and R^(b2) combine to each other,together with the nitrogen atom to which they bind, to form a cyclicamino group are referred to as “cyclicamino-carbonyl-oxy group.”

Among the groups represented by the formula (ω-11B), those groups inwhich R^(a2) is a hydrocarbon group are referred to as“N-hydrocarbon-thiocarbamoyl-oxy group,” and those groups in whichR^(a2) is a heterocyclic group are referred to as “N-heterocyclicring-thiocarbamoyl-oxy group.”

Among the groups represented by the formula (ω-12B), those groups inwhich both R^(a2) and R^(b2) are hydrocarbon groups are referred to as“N,N-di(hydrocarbon)-thiocarbamoyl-oxy group,” those groups in whichboth R^(a2) and R^(b2) are heterocyclic groups are referred to as“N,N-di(heterocyclic ring)-thiocarbamoyl-oxy group,” those groups inwhich R^(a2) is a hydrocarbon group and R^(b2) is a heterocyclic groupare referred to as “N-hydrocarbon-N-heterocyclic ring-thiocarbamoyl-oxygroup,” and those groups in which R^(a2) and R^(b2) combine to eachother, together with the nitrogen atom to which they bind, to form acyclic amino group are referred to as “cyclicamino-thiocarbonyl-oxygroup.”

Among the groups represented by the formula (ω-13B), those groups inwhich R^(a2) is a hydrocarbon group are referred to as“N-hydrocarbon-sulfamoyl-oxy group,” and those groups in which R^(a2) isa heterocyclic group are referred to as “N-heterocyclicring-sulfamoyl-oxy group.”

Among the groups represented by the formula (ω-14B), those groups inwhich both R^(a2) and R^(b2) are hydrocarbon groups are referred to as“N,N-di(hydrocarbon)-sulfamoyl-oxy group,” those groups in which bothR^(a2) and R^(b2) are heterocyclic groups are referred to as“N,N-di(heterocyclic ring)-sulfamoyl-oxy group,” those groups in whichR^(a2) is a hydrocarbon group and R^(b2) is a heterocyclic group arereferred to as “N-hydrocarbon-N-heterocyclic ring-sulfamoyl-oxy group,”and those groups in which R^(a2) and R^(b2) combine to each other,together with the nitrogen atom to which they bind, to form a cyclicamino group are referred to as “cyclic amino-sulfonyl-oxy group.”

Among the groups represented by the formula (ω-15B), those groups inwhich R^(a2) is a hydrocarbon group are referred to as“N-hydrocarbon-sulfinamoyl-oxy group,” and those groups where R^(a2) isa heterocyclic group are referred to as “N-heterocyclicring-sulfinamoyl-oxy group.”

Among the groups represented by the formula (ω-16B), those groups inwhich both R^(a2) and R^(b2) are hydrocarbon groups are referred to as“N,N-di(hydrocarbon)-sulfinamoyl-oxy group,” those groups in which bothR^(a2) and R^(b2) are heterocyclic groups are referred to as“N,N-di(heterocyclic ring)-sulfinamoyl-oxy group,” those groups in whichR^(a2) is a hydrocarbon group and R^(b2) is a heterocyclic group arereferred to as “N-hydrocarbon-N-heterocyclic ring-sulfinamoyl-oxygroup,” and those groups in which R^(a2) and R^(b2) combine to eachother, together with the nitrogen atom to which they bind, to form acyclic amino group are referred to as “cyclic amino-sulfinyl-oxy group.”

Among the groups represented by the formula (ω-17B), those groups inwhich R^(a2) is a hydrocarbon group are referred to as“hydrocarbon-oxy-sulfonyl-oxy group,” and those groups in which R^(a2)is a heterocyclic group are referred to as “heterocyclicring-oxy-sulfonyl-oxy group.”

Among the groups represented by the formula (ω-18B), those groups inwhich R^(a2) is a hydrocarbon group are referred to as“hydrocarbon-oxy-sulfinyl-oxy group,” those groups in which R^(a2) is aheterocyclic group are referred to as “heterocyclicring-oxy-sulfinyl-oxy group.”

Among the groups represented by the formula (ω-19B), those groups inwhich both R^(a2) and R^(b2) are hydrocarbon groups are referred to as“O,O′-di(hydrocarbon)-phosphono-oxy group,” those groups in which bothR^(a2) and R^(b2) are heterocyclic groups are referred to as“O,O′-di(heterocyclic ring)-phosphono-oxy group,” and those groups inwhich R^(a2) is a hydrocarbon group and R^(b2) is a heterocyclic groupare referred to as “O-hydrocarbon substituted-O′-heterocyclic ringsubstituted phosphono-oxy group.”

Among the groups represented by the formula (ω-20B), those groups inwhich R^(a2) is a hydrocarbon group are referred to as“hydrocarbon-sulfonyl-oxy group,” and those groups in which R^(a2) is aheterocyclic group referred to as “heterocyclic ring-sulfonyl-oxygroup.”

Among the groups represented by the formula (ω-21B), those groups inwhich R^(a2) is a hydrocarbon group are referred to as“hydrocarbon-sulfinyl-oxy group,” and those groups in which R^(a2) is aheterocyclic group are referred to as “heterocyclic ring-sulfinyl-oxygroup.”

Examples of the hydrocarbon in the groups represented by theaforementioned formulas (ω-1B) through (ω-21B) include the similargroups to the aforementioned hydrocarbon group. Examples of thehydrocarbon-carbonyl-oxy group represented by the formula (ω-1B)include, for example, an alkyl-carbonyl-oxy group, analkenyl-carbonyl-oxy group, an alkynyl-carbonyl-oxy group, acycloalkyl-carbonyl-oxy group, a cycloalkenyl-carbonyl-oxy group, acycloalkanedienyl-carbonyl-oxy group, and acycloalkyl-alkyl-carbonyl-oxy group, which are aliphatichydrocarbon-carbonyl-oxy groups; an aryl-carbonyl-oxy group; anaralkyl-carbonyl-oxy group; a bridged cyclic hydrocarbon-carbonyl-oxygroup; a spirocyclic hydrocarbon-carbonyl-oxy group; and a terpenefamily hydrocarbon-carbonyl-oxy group. In the following descriptions,groups represented by the formulas (ω-2B) through (ω-21B) are similar tothose explained above.

Examples of the heterocyclic ring in the groups represented by theaforementioned formulas (ω-1B) through (ω-21B) include similar groups tothe aforementioned heterocyclic group. Examples of the heterocyclicring-carbonyl group represented by the formula (ω-1B) include, forexample, a monocyclic heteroaryl-carbonyl group, a fused polycyclicheteroaryl-carbonyl group, a monocyclic non-aromatic heterocyclicring-carbonyl group, and a fused polycyclic non-aromatic heterocyclicring-carbonyl group. In the following descriptions, groups representedby the formulas (ω-2B) through (ω-21B) are similar to those groupsexplained above.

Examples of the cyclic amino in the groups represented by theaforementioned formulas (ω-10B) through (ω-16B) include similar groupsto the aforementioned cyclic amino group.

The aforementioned acyl-oxy group, hydrocarbon-oxy group, andheterocyclic-oxy group are generically referred to as “substituted oxygroup.” Moreover, these substituted oxy group and hydroxy group aregenerically referred to as “hydroxy group which may be substituted.”

Examples of the acyl-sulfanyl group include the groups in which hydrogenatom of sulfanyl group is substituted with acyl group, and include, forexample, formylsulfanyl group, glyoxyloylsulfanyl group,thioformylsulfanyl group, and groups represented by the followingformulas:

wherein each of R^(a3)and R^(b3) independently represents a hydrocarbongroup or a heterocyclic group, or when each of R^(a3) and R^(b3) bindsto the same nitrogen atom, R^(a3) and R^(b3) may combine to each other,together with the nitrogen atom to which they bind, to form a cyclicamino group.

In the definition of the aforementioned acyl-sulfanyl group, among thegroups represented by the formula (ω-1C), those groups in which R^(a3)is a hydrocarbon group are referred to as “hydrocarbon-carbonyl-sulfanylgroup,” and those groups in which R^(a3) is a heterocyclic group arereferred to as “heterocyclic ring-carbonyl-sulfanyl group.”

Among the groups represented by the formula (ω-2C), those groups inwhich R^(a3) is a hydrocarbon group are referred to as“hydrocarbon-oxy-carbonyl-sulfanyl group,” and those groups in whichR^(a3) is a heterocyclic group are referred to as “heterocyclicring-oxy-carbonyl-sulfanyl group.”

Among the groups represented by the formula (ω-3C), those groups inwhich R^(a3) is a hydrocarbon group are referred to as“hydrocarbon-carbonyl-carbonyl-sulfanyl group,” and those groups inwhich R^(a3) is a heterocyclic group are referred to as “heterocyclicring-carbonyl-carbonyl-sulfanyl group.”

Among the groups represented by the formula (ω-4C), those groups inwhich R^(a3) is a hydrocarbon group are referred to as“hydrocarbon-oxy-carbonyl-carbonyl-sulfanyl group,” and those groups inwhich R^(a3) is a heterocyclic group are referred to as “heterocyclicring-oxy-carbonyl-carbonyl-sulfanyl group.”

Among the groups represented by the formula (ω-5C), those groups inwhich R^(a3) is a hydrocarbon group are referred to as“hydrocarbon-sulfanyl-carbonyl-sulfanyl group,” and those groups inwhich R^(a3) is a heterocyclic group are referred to as “heterocyclicring-sulfanyl-carbonyl-sulfanyl group.”

Among the groups represented by the formula (ω-6C), those groups inwhich R^(a3) is a hydrocarbon group are referred to as“hydrocarbon-thiocarbonyl-sulfanyl group,” and those groups in whichR^(a3) is a heterocyclic group are referred to as “heterocyclicring-thiocarbonyl-sulfanyl group.”

Among the groups represented by the formula (ω-7C), those groups inwhich R^(a3) is a hydrocarbon group are referred to as“hydrocarbon-oxy-thiocarbonyl-sulfanyl group,” and those groups in whichR^(a3) is a heterocyclic group are referred to as “heterocyclicring-oxy-thiocarbonyl-sulfanyl group.”

Among the groups represented by the formula (ω-8C), those groups inwhich R^(a3) is a hydrocarbon group are referred to as“hydrocarbon-sulfanyl-thiocarbonyl-sulfanyl group,” and those groups inwhich R^(a3) is a heterocyclic group are referred to as “heterocyclicring-sulfanyl-thiocarbonyl-sulfanyl group.”

Among the groups represented by the formula (ω-9C), those groups inwhich R^(a3) is a hydrocarbon group are referred to as“N-hydrocarbon-carbamoyl-sulfanyl group,” and those groups in whichR^(a3) is a heterocyclic group are referred to as “N-heterocyclicring-carbamoyl-sulfanyl group.”

Among the groups represented by the formula (ω-10C), those groups inwhich both R^(a3) and R^(b3) are a hydrocarbon groups are referred to as“N,N-di(hydrocarbon)-carbamoyl-sulfanyl group,” those groups in whichboth R^(a3) and R^(b3) are heterocyclic groups are referred to as“N,N-di(heterocyclic ring)-carbamoyl-sulfanyl group,” those groups inwhich R^(a3) is a hydrocarbon group and R^(b3) is a heterocyclic groupare referred to as “N-hydrocarbon-N-heterocyclic ring-carbamoyl-sulfanylgroup,” and those groups in which R^(a3) and R^(b3) combine to eachother, together with the nitrogen atom to which they bind, to form acyclic amino group are referred to as “cyclicamino-carbonyl-sulfamoylgroup.”

Among the groups represented by the formula (ω-11C), those groups inwhich R^(a3) is a hydrocarbon group are referred to as“N-hydrocarbon-thiocarbamoyl-sulfanyl group,” and those groups in whichR^(a3) is a heterocyclic group are referred to as “N-heterocyclicring-thiocarbamoyl-sulfanyl group.”

Among the groups represented by the formula (ω-12C), those groups inwhich both R^(a3) and R^(b3) are hydrocarbon groups are referred to as“N,N-di(hydrocarbon)-thiocarbamoyl-sulfanyl group,” those groups inwhich and R^(a3) and R^(b3) are heterocyclic groups are referred to as“N,N-di(heterocyclic ring)-thiocarbamoyl-sulfanyl group,” those groupsin which R^(a3) is a hydrocarbon group and R^(b3) is a heterocyclicgroup are referred to as “N-hydrocarbon-N-heterocyclicring-thiocarbamoyl-sulfanyl group,” and those groups in which R^(a3) andR^(b3) combine to each other, together with the nitrogen atom to whichthey bind, to form a cyclic amino group are referred to as“cyclicamino-thiocarbonyl-sulfamoyl group.”

Among the groups represented by the formula (ω-13C), those groups inwhich R^(a3) is a hydrocarbon group are referred to as“N-hydrocarbon-sulfamoyl-sulfanyl group,” and those groups in whichR^(a3) is a heterocyclic group are referred to as “N-heterocyclicring-sulfamoyl-sulfanyl group.”

Among the groups represented by the formula (ω-14C), those groups inwhich both R^(a3) and R^(b3) are hydrocarbon groups are referred to as“N,N-di(hydrocarbon)-sulfamoyl-sulfanyl group,” those groups in whichboth R^(a3) and R^(b3) are heterocyclic groups are referred to as“N,N-di(heterocyclic ring)-sulfamoyl-sulfinyl group,” those groups inwhich R^(a3) is a hydrocarbon group and R^(b3) is a heterocyclic groupare referred to as “N-hydrocarbon-N-heterocyclic ring-sulfamoyl-sulfanylgroup,” and those groups in which R^(a3) and R^(b3) combine to eachother, together with the nitrogen atom to which they bind, to form acyclic amino group are referred to as “cyclicamino-sulfonyl-sulfanylgroup.”

Among the groups represented by the formula (ω-15C), those groups inwhich R^(a3) is a hydrocarbon group are referred to as“N-hydrocarbon-sulfinamoyl-sulfanyl group,” and those groups in whichR^(a3) is a heterocyclic group are referred to as “N-heterocyclicring-sulfinamoyl-sulfanyl group.”

Among the groups represented by the formula (ω-16C), those groups inwhich both R^(a3) and R^(b3) are hydrocarbon groups are referred to as“N,N-di(hydrocarbon)-sulfinamoyl-sulfanyl group,” those groups in whichboth R^(a3) and R^(b3) are heterocyclic groups are referred to as“N,N-di(heterocyclic ring)-sulfinamoyl-sulfanyl group,” those groups inwhich R^(a3) is a hydrocarbon group and R^(b3) is a heterocyclic groupare referred to as “N-hydrocarbon-N-heterocyclicring-sulfinamoyl-sulfanyl group,” and those groups in which R^(a3) andR^(b3) combine to each other, together with the nitrogen atom to whichthey bind, to form a cyclic amino group are referred to as“cyclicamino-sulfanyl-sulfanyl group.”

Among the groups represented by the formula (ω-17C), those groups inwhich R^(a3) is a hydrocarbon group are referred to as“hydrocarbon-oxy-sulfonyl-sulfanyl group,” and those groups in whichR^(a3) is a heterocyclic group are referred to as “heterocyclicring-oxy-sulfonyl-sulfanyl group.”

Among the groups represented by the formula (ω-18C), those groups inwhich R^(a3) is a hydrocarbon group are referred to as“hydrocarbon-oxy-sulfinyl-sulfanyl group,” and those groups in whichR^(a3) is a heterocyclic group are referred to as “heterocyclicring-oxy-sulfinyl-sulfanyl group.”

Among the groups represented by the formula (ω-19C), those groups inwhich both R^(a3) and R^(b3) are hydrocarbon groups are referred to as“O,O′-di(hydrocarbon)-phosphono-sulfanyl group,” those groups in whichboth R^(a3) and R^(b3) are heterocyclic groups are referred to as“O,O′-di(heterocyclic ring)-phosphono-sulfanyl group,” and those groupsin which R^(a3) is a hydrocarbon group and R^(b3) is a heterocyclicgroup are referred to as “O-hydrocarbon-O′-heterocyclicring-phosphono-sulfanyl group.”

Among the groups represented by the formula (ω-20C), those groups inwhich R^(a3) is a hydrocarbon group are referred to as“hydrocarbon-sulfonyl-sulfanyl group,” and those groups in which R^(a3)is a heterocyclic group are referred to as “heterocyclicring-sulfonyl-sulfanyl group.”

Among the groups represented by the formula (ω-21C), those groups inwhich R^(a3) is a hydrocarbon group are referred to as“hydrocarbon-sulfinyl-sulfanyl group,” and those groups in which R^(a3)is a heterocyclic group are referred to as “heterocyclicring-sulfinyl-sulfanyl group.”

Examples of the hydrocarbon in the groups represented by theaforementioned formulas (ω-1C) through (ω-21C) include similar groups tothe aforementioned hydrocarbon group. Examples of thehydrocarbon-carbonyl-sulfanyl group represented by the formula (ω-1C)include, for example, an alkyl-carbonyl-sulfanyl group, analkenyl-carbonyl-sulfanyl group, an alkynyl-carbonyl-sulfanyl group, acycloalkyl-carbonyl-sulfanyl group, a cycloalkenyl-carbonyl-sulfanylgroup, a cycloalkanedienyl-carbonyl-sulfanyl group, acycloalkyl-alkyl-carbonyl-sulfanyl group which are aliphatichydrocarbon-carbonyl-sulfanyl groups; an aryl-carbonyl-sulfanyl group;an aralkyl-carbonyl-sulfanyl group; a bridged cyclichydrocarbon-carbonyl-sulfanyl group; a spiro cyclichydrocarbon-carbonyl-sulfanyl group; and a terpene familyhydrocarbon-carbonyl-sulfanyl group. In the following descriptions,groups represented by the formulas (ω-2C) through (ω-21C) are similar tothose explained above.

Examples of the heterocyclic ring in the groups represented by theaforementioned formulas (ω-1C) through (ω-21C) include similar groups tothe aforementioned heterocyclic group. Examples of the heterocyclicring-carbonyl-sulfanyl group represented by the formula (ω-1C) include,for example, a monocyclic heteroaryl-carbonyl-sulfanyl group, a fusedpolycyclic heteroaryl-carbonyl-sulfanyl group, a monocyclic non-aromaticheterocyclic ring-carbonyl-sulfanyl group, and a fused polycyclicnon-aromatic heterocyclic ring-carbonyl-sulfanyl group. In the followingdescriptions, groups represented by the formula (ω-2C) through (ω-21C)are similar to those groups explained above.

Examples of the cyclic amino in the groups represented by theaforementioned formulas (ω-10C) through (ω-16C) include similar groupsto the aforementioned cyclic amino group.

The aforementioned acyl-sulfanyl group, hydrocarbon-sulfanyl group, andheterocyclic-sulfanyl group are generically referred to as “substitutedsulfanyl group.” Moreover, these substituted sulfanyl group and sulfanylgroup are generically referred to as “sulfanyl group which may besubstituted.”

Examples of the N-hydrocarbon-amino group include the groups in whichone hydrogen atom of amino group is substituted with a hydrocarbongroup, and include, for example, an N-alkyl-amino group, anN-alkenyl-amino group, an N-alkynyl-amino group, an N-cycloalkyl-aminogroup, an N-cycloalkyl-alkyl-amino group, an N-aryl-amino group, and anN-aralkyl-amino group.

Examples of the N-alkyl-amino group include, for example, methylamino,ethylamino, n-propylamino, isopropylamino, n-butylamino, isobutylamino,sec-butylamino, tert-butylamino, n-pentylamino, isopentylamino,(2-methylbutyl)amino, (1-methylbutyl)amino, neopentylamino,(1,2-dimethylpropyl)amino, (1-ethylpropyl)amino, n-hexylamino,(4-methylpentyl)amino, (3-methylpentyl)amino, (2-methylpentyl)amino,(1-methylpentyl)amino, (3,3-dimethylbutyl)amino,(2,2-dimethylbutyl)amino, (1,1-dimethylbutyl)amino,(1,2-dimethylbutyl)amino, (1,3-dimethylbutyl)amino,(2,3-dimethylbutyl)amino, (2-ethylbutyl)amino, (1-ethylbutyl)amino,(1-ethyl-1-methylpropyl)amino, n-heptylamino, n-octylamino,n-nonylamino, n-decylamino, n-undecylamino, n-dodecylamino,n-tridecylamino, n-tetradecylamino, and n-pentadecylamino, which are C₁to C₁₅ straight chain or branched chain N-alkyl amino groups.

Examples of the N-alkenyl-amino group include, for example, vinyl amino,(prop-1-en-1-yl)amino, allylamino, isopropenylamino,(but-1-en-1-yl)amino, (but-2-en-1-yl)amino, (but-3-en-1-yl)amino,(2-methylprop-2-en-1-yl)amino, (1-methylprop-2-en-1-yl)amino,(pent-1-en-1-yl)amino, (pent-2-en-1-yl)amino, (pent-3-en-1-yl)amino,(pent-4-en-1-yl)amino, (3-methylbut-2-en-1-yl)amino,(3-methylbut-3-en-1-yl)amino, (hex-1-en-1-yl)amino,(hex-2-en-1-yl)amino, (hex-3-en-1-yl)amino, (hex-4-en-1-yl)amino,(hex-5-en-1-yl)amino, (4-methylpent-3-en-1-yl)amino,(4-methylpent-3-en-1-yl)amino, (hept-1-en-1-yl)amino,(hept-6-en-1-yl)amino, (oct-1-en-1-yl)amino, (oct-7-en-1-yl)amino,(non-1-en-1-yl)amino, (non-8-en-1-yl)amino, (dec-1-en-1-yl)amino,(dec-9-en-1-yl)amino, (undec-1-en-1-yl)amino, (undec-10-en-1-yl)amino,(dodec-1-en-1-yl)amino, (dodec-11-en-1-yl)amino,(tridec-1-en-1-yl)amino, (tridec-12-en-1-yl)amino,(tetradec-1-en-1-yl)amino, (tetradec-13-en-1-yl)amino,(pentadec-1-en-1-yl)amino, and (pentadec-14-en-1-yl)amino, which are C₂to C₁₅ straight chain or branched chain N-alkenyl amino groups.

Examples of the N-alkynyl-amino group include, for example,ethynylamino, (prop-1-yn-1-yl)amino, (prop-2-yn-1-yl)amino,(but-1-yn-1-yl)amino, (but-3-yn-1-yl)amino,(1-methylprop-2-yn-1-yl)amino, (pent-1-yn-1-yl)amino,(pent-4-yn-1-yl)amino, (hex-1-yn-1-yl)amino, (hex-5-yn-1-yl)amino,(hept-1-yn-1-yl)amino, (hept-6-yn-1-yl)amino, (oct-1-yn-1-yl)amino,(oct-7-yn-1-yl)amino, (non-1-yn-1-yl)amino, (non-8-yn-1-yl)amino,(dec-1-yn-1-yl)amino, (dec-9-yn-1-yl)amino, (undec-1-yn-1-yl)amino,(undec-10-yn-1-yl)amino, (dodec-1-yn-1-yl)amino,(dodec-11-yn-1-yl)amino, (tridec-1-yn-1-yl)amino,(tridec-12-yn-1-yl)amino, (tetradec-1-yn-1-yl)amino,(tetradec-13-yn-1-yl)amino, (pentadec-1-yn-1-yl)amino, and(pentadec-14-yn-1-yl)amino, which are C₂ to C₁₅ straight chain orbranched chain N-alkynyl-amino groups.

Examples of the N-cycloalkyl-amino group include, for example,cyclopropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino,cycloheptylamino, and cyclooctylamino, which are C₃ to C₈N-cycloalkyl-amino groups.

Examples of the N-cycloalkyl-alkyl-amino group include, for example,(cyclopropylmethyl)amino, (1-cyclopropylethyl)amino,(2-cyclopropylethyl)amino, (3-cyclopropylpropyl)amino,(4-cyclopropylbutyl)amino, (5-cyclopropylpentyl)amino,(6-cyclopropylhexyl)amino, (cyclobutylmethyl)amino,(cyclopentylmethyl)amino, (cyclobutylmethyl)amino,(cyclopentylmethyl)amino, (cyclohexylmethyl)amino,(2-cyclohexylethyl)amino, (3-cyclohexylpropyl)amino,(4-cyclohexylbutyl)amino, (cycloheptylmethyl)amino,(cyclooctylmethyl)amino, and (6-cyclooctylhexyl)amino, which are C₄ toC₁₄ N-cycloalkyl-alkyl-amino groups.

Examples of the N-aryl-amino group include, for example, phenylamino,1-naphthylamino, 2-naphtylamino, anthrylamino, phenanthrylamino, andacenaphthylenylamino, which are C₆ to C₁₄ N-mono-arylamino groups.

Examples of the N-aralkyl-amino group include, for example, benzylamino,(1-naphthylmethyl)amino, (2-naphthylmethyl)amino,(anthracenylmethyl)amino, (phenanthrenylmethyl)amino,(acenaphthylenylmethyl)amino, (diphenylmethyl)amino, (1-phenethyl)amino,(2-phenethyl)amino, (1-(1-naphthyl)ethyl)amino,(1-(2-naphthyl)ethyl)amino, (2-(1-naphthyl)ethyl)amino,(2-(2-naphthyl)ethyl)amino, (3-phenylpropyl)amino,(3-(1-naphthyl)propyl)amino, (3-(2-naphthyl)propyl)amino,(4-phenylbutyl)amino, (4-(1-naphthyl)butyl)amino,(4-(2-naphthyl)butyl)amino, (5-phenylpentyl)amino,(5-(1-naphthyl)pentyl)amino, (5-(2-naphthyl)pentyl)amino,(6-phenylhexyl)amino, (6-(1-naphthyl)hexyl)amino, and(6-(2-naphthyl)hexyl)amino, which are C₇ to C₁₆ N-aralkyl-amino groups.

Examples of the N,N-di(hydrocarbon)-amino group include the groups inwhich two hydrogen atoms of amino group are substituted with hydrocarbongroups, and include, for example, N,N-dimethylamino, N,N-diethylamino,N-ethyl-N-methylamino, N,N-di-n-propylamino, N,N-diisopropylamino,N-allyl-N-methylamino, N-(prop-2-yn-1-yl)-N-methylamino,N,N-dicyclohexylamino, N-cyclohexyl-N-methylamino,N-cyclohexylmethylamino-N-methylamino, N,N-diphenylamino,N-methyl-N-phenylamino, N,N-dibenzylamino, and N-benzyl-N-methylamino.

Examples of the N-heterocyclic ring-amino group include the groups inwhich one hydrogen atom of amino group is substituted with aheterocyclic group, and include, for example, (3-pyrrolidinyl)amino,(4-piperidinyl)amino, (2-tetrahydropyranyl)amino, (3-indolinyl)amino,(4-chromanyl)amino, (3-thienyl)amino, (3-pyridyl)amino,(3-quinolyl)amino, and (5-indolyl)amino.

Examples of the N-hydrocarbon-N-heterocyclic ring-amino group includethe groups in which two hydrogen atoms of amino group are substitutedwith hydrocarbon group and heterocyclic group respectively, and include,for example, N-methyl-N-(4-piperidinyl)amino,N-(4-chromanyl)-N-methylamino, N-methyl-N-(3-thienyl)amino,N-methyl-N-(3-pyridyl)amino, N-methyl-N-(3-quinolyl)amino.

Examples of the acyl-amino group include the groups in which onehydrogen atom of the amino group is substituted with an acyl group, andinclude, for example, formylamino group, glyoxyloylamino group,thioformylamino group, and groups represented by the following formulas:

wherein each of R¹⁴ and R^(b4) independently represents a hydrocarbongroup or a heterocyclic group, or when each of R^(a4) and R^(b4) bindsto the same nitrogen atom, R^(a4) and R^(b4) may combine to each other,together with the nitrogen atom to which they bind, to form a cyclicamino group.

In the definition of the aforementioned acyl-amino group, among thegroups represented by the formula (ω-1D), those groups in which R^(a4)is a hydrocarbon group are referred to as “hydrocarbon-carbonyl-aminogroup,” and those groups in which R^(a4) is a heterocyclic group arereferred to as “heterocyclic ring-carbonyl-amino group.”

Among the groups represented by the formula (ω-2D), those groups inwhich R^(a4) is a hydrocarbon group are referred to as“hydrocarbon-oxy-carbonyl-amino group,” and those groups in which R^(a4)is a heterocyclic group are referred to as “heterocyclicring-oxy-carbonyl-amino group.”

Among the groups represented by the formula (ω-3D), those groups inwhich R^(a4) is a hydrocarbon group are referred to as“hydrocarbon-carbonyl-carbonyl-amino group,” and those groups in whichR^(a4) is a heterocyclic group are referred to as “heterocyclicring-carbonyl-carbonyl-amino group.”

Among the groups represented by the formula (ω-4D), those groups inwhich R^(a4) is a hydrocarbon group are referred to as“hydrocarbon-oxy-carbonyl-carbonyl-amino group,” and those groups inwhich R^(a4) is a heterocyclic group are referred to as “heterocyclicring-oxy-carbonyl-carbonyl-amino group.”

Among the groups represented by the formula (ω-5D), those groups inwhich R^(a4) is a hydrocarbon group are referred to as“hydrocarbon-sulfanyl-carbonyl-amino group,” and those groups in whichR^(a4) is a heterocyclic group are referred to as “heterocyclicring-sulfanyl-carbonyl-amino group.”

Among the groups represented by the formula (ω-6D), those groups inwhich R^(a4) is a hydrocarbon group are referred to as“hydrocarbon-thiocarbonyl-amino group,” and those groups in which R^(a4)is a heterocyclic group are referred to as “heterocyclicring-thiocarbonyl-amino group.”

Among the groups represented by the formula (ω-7D), those groups inwhich R^(a4) is a hydrocarbon group are referred to as“hydrocarbon-oxy-thiocarbonyl-amino group,” and those groups in whichR^(a4) is a heterocyclic group are referred to as “heterocyclicring-oxy-thiocarbonyl-amino group.”

Among the groups represented by the formula (ω-8D), those groups inwhich R^(a4) is a hydrocarbon group are referred to as“hydrocarbon-sulfanyl-thiocarbonyl-amino group,” and those groups inwhich R^(a4) is a heterocyclic group are referred to as “heterocyclicring-sulfanyl-thiocarbonyl-amino group.”

Among the groups represented by the formula (ω-9D), those groups inwhich R^(a4) is a hydrocarbon group are referred to as“N-hydrocarbon-carbamoyl group,” and those groups in which R^(a4) is aheterocyclic group are referred to as “N-heterocyclicring-carbamoyl-amino group.”

Among the groups represented by the formula (ω-10D), those groups inwhich both R^(a4) and R^(b4) are hydrocarbon groups are referred to as“N,N-di(hydrocarbon)-carbamoyl-amino group,” those groups in which bothR^(a4) and R^(b4) are heterocyclic groups are referred to as“N,N-di(heterocyclic ring)-carbamoyl-amino group,” those groups in whichR^(a4) is a hydrocarbon group and R^(b4) is a heterocyclic group arereferred to as “N-hydrocarbon-N-heterocyclic ring-carbamoyl-aminogroup,” and those groups in which R^(a4) and R^(b4) combine to eachother, together with the nitrogen atom to which they bind, to form acyclic amino group are referred to as “cyclic amino-carbonyl-aminogroup.”

Among the groups represented by the formula (ω-11D), those groups inwhich Ra⁴ is a hydrocarbon group are referred to as“N-hydrocarbon-thiocarbamoyl-amino group,” and those groups in whichR^(a4) is a heterocyclic ring group are referred to as“N-heterocyclic-thiocarbamoyl-amino group.”

Among the groups represented by the formula (ω-12D), those groups inwhich both R^(a4) and R^(b4) are hydrocarbon groups are referred to as“N,N-di(hydrocarbon)-thiocarbamoyl-amino group,” those groups in whichboth R^(a4) and R^(b4) are heterocyclic groups are referred to as“N,N-di(heterocyclic ring)-thiocarbamoyl-amino group,” those groups inwhich R^(a4) is a hydrocarbon group and R^(b4) is a heterocyclic groupare referred to as “N-hydrocarbon-N-heterocyclicring-thiocarbamoyl-amino group,” and those groups in which R^(a4) andR^(b4) combine to each other, together with the nitrogen atom to whichthey bind, to form a cyclic amino group are referred to as “cyclicamino-thiocarbonyl-amino group.”

Among the groups represented by the formula (ω-13D), those groups inwhich R^(a4) is a hydrocarbon group are referred to as“N-hydrocarbon-sulfamoyl-amino group,” and those groups in which R^(a4)is a heterocyclic group are referred to as “N-heterocyclicring-sulfamoyl-amino group.”

Among the groups represented by the formula (ω-14D), those groups inwhich both R^(a4) and R^(b4) are hydrocarbon groups are referred to as“di(hydrocarbon)-sulfamoyl-amino group,” those groups in which bothR^(a4) and R^(b4) are heterocyclic groups are referred to as“N,N-di(heterocyclic ring)-sulfamoyl-amino group,” those groups in whichR^(a4) is a hydrocarbon group and R^(b4) is a heterocyclic group arereferred to as “N-hydrocarbon-N-heterocyclic ring-sulfamoyl-aminogroup,” and those groups in which R^(a4) and R^(b4) combine to eachother, together with the nitrogen atom to which they bind, to form acyclic amino group are referred to as “cyclic amino-sulfonyl-aminogroup.”

Among the groups represented by the formula (ω-15D), those groups inwhich R^(a4) is a hydrocarbon group are referred to as“N-hydrocarbon-sulfinamoyl-amino group,” and those groups in whichR^(a4) is a heterocyclic group are referred to as “N-heterocyclicring-sulfinamoyl-amino group.”

Among the groups represented by the formula (ω-16D), those groups inwhich both R^(a4) and R^(b4) are hydrocarbon groups are referred to as“N,N-di(hydrocarbon)-sulfinamoyl-amino group,” those groups in whichboth R^(a4) and R^(b4) are heterocyclic groups are referred to as“N,N-di(heterocyclic ring)-sulfinamoyl-amino group,” groups in whichR^(a4) is a hydrocarbon group and R^(b4) is a heterocyclic group arereferred to as “N-hydrocarbon-N-heterocyclic ring-sulfinamoyl-aminogroup,” and those groups in which R^(a4) and R^(b4) combine to eachother, together with the nitrogen atom to which they bind, to form acyclic amino group are referred to as “cyclic amino-sulfinyl-aminogroup.”

Among the groups represented by the formula (ω-17D), those groups inwhich R^(a4) is a hydrocarbon group are referred to as“hydrocarbon-oxy-sulfonyl-amino group,” and those groups in which R^(a4)is a heterocyclic group are referred to as “heterocyclicring-oxy-sulfoyl-amino group.”

Among the groups represented by the formula (ω-18D), those groups inwhich R^(a4) is a hydrocarbon group are referred to as“hydrocarbon-oxy-sulfinyl-amino group,” and those groups in which R^(a4)is a heterocyclic group are referred to as “heterocyclicring-oxy-sulfinyl-amino group.”

Among the groups represented by the formula (ω-19D), those groups inwhich both R^(a4) and R^(b4) are hydrocarbon groups are referred to as“O,O′-di(hydrocarbon)-phosphono-amino group,” those groups in which bothR^(a4) and R^(b4) are heterocyclic groups are referred to as“O,O′-di(heterocyclic ring)-phosphono-amino group,” and those groups inwhich R^(a4) is a hydrocarbon group and R^(b4) is a heterocyclic groupare referred to as “O-hydrocarbon-O′-heterocyclic ring-phosphono-aminogroup.”

Among the groups represented by the formula (ω-20D), those groups inwhich R^(a4) is a hydrocarbon group are referred to as“hydrocarbon-sulfonyl-amino group,” and those groups in which R^(a4) isa heterocyclic group are referred to as “heterocyclicring-sulfonyl-amino group.”

Among the groups represented by the formula (ω-21D), those groups inwhich R^(a4) is a hydrocarbon group are referred to as“hydrocarbon-sulfinyl-amino group,” and those groups in which R^(a4) isa heterocyclic group are referred to as “heterocyclicring-sulfinyl-amino group.”

Examples of the hydrocarbon in the groups represented by theaforementioned formulas (ω-1D) through (ω-21D) include the similargroups to the aforementioned hydrocarbon group. Examples of thehydrocarbon-carbonyl-amino groups represented by the formula (ω-1D)include, for example, an alkyl-carbonyl-amino group, analkenyl-carbonyl-amino group, an alkynyl-carbonyl-amino group, acycloalkyl-carbonyl-amino group, a cycloalkenyl-carbonyl-amino group, acycloalkanedienyl-carbonyl-amino group, acycloalkyl-alkyl-carbonyl-amino group which are aliphatichydrocarbon-carbonyl-amino groups; an aryl-carbonyl-amino group; anaralkyl-carbonyl-amino group; a bridged cyclichydrocarbon-carbonyl-amino group; a spiro cyclichydrocarbon-carbonyl-amino group; and a terpene familyhydrocarbon-carbonyl-amino group. In the following descriptions, groupsrepresented by the formulas (ω-2D) through (ω-21D) are similar to thoseexplained above.

Examples of the heterocyclic ring in the groups represented by theaforementioned formulas (ω-1D) through (ω-21D) include similar groups tothe aforementioned heterocyclic group. Examples of the heterocyclicring-carbonyl-amino group represented by the formula (ω-1D) include, forexample, a monocyclic heteroaryl-carbonyl-amino group, a fusedpolycyclic heteroaryl-carbonyl-amino group, a monocyclic non-aromaticheterocyclic-carbonyl-amino group, and a fused polycyclic non-aromaticheterocyclic-carbonyl-amino group. In the following descriptions, groupsrepresented by the formulas (ω-2D) through (ω-21D) are similar to thosegroups explained above.

Examples of the cyclic amino in the groups represented by theaforementioned formulas (ω-10D) through (ω-16D) include similar groupsto the aforementioned cyclic amino group.

Examples of the di(acyl)-amino group include the groups in which twohydrogen atoms of amino group are substituted with acyl groups in thedefinitions of the aforementioned substituents according to “which maybe substituted.” Examples include, for example, di(formyl)-amino group,di(glyoxyloyl)-amino group, di(thioformyl)-amino group, and groupsrepresented by the following formulas:

wherein each of R^(a5) and R^(b5) independently represents a hydrocarbongroup or a heterocyclic group, or when each of R^(a5) and R^(b5) bindsto the same nitrogen atom, R^(a5) and R^(b5) may combine to each other,together with the nitrogen atom to which they bind, to form a cyclicamino group.

In the definition of aforementioned di(acyl)-amino group, among thegroups represented by the formula (ω-1E), those groups in which R^(a5)is a hydrocarbon group are referred to as“bis(hydrocarbon-carbonyl)-amino group,” and those groups in whichR^(a5) is a heterocyclic group are referred to as “bis(heterocyclicring-carbonyl)-amino group.”

Among the groups represented by the formula (ω-2E), those groups inwhich R^(a5) is a hydrocarbon group are referred to as“bis(hydrocarbon-oxy-carbonyl)-amino group,” and those groups in whichR^(a5) is a heterocyclic group are referred to as “bis(heterocyclicring-oxy-carbonyl)-amino group.”

Among the groups represented by the formula (ω-3E), those groups inwhich R^(a5) is a hydrocarbon group are referred to as“bis(hydrocarbon-carbonyl-carbonyl)-amino group,” and those groups inwhich R^(a5) is a heterocyclic group are referred to as“bis(heterocyclic ring-carbonyl-carbonyl)-amino group.”

Among the groups represented by the formula (ω-4E), those groups inwhich R^(a5) is a hydrocarbon group are referred to as“bis(hydrocarbon-oxy-carbonyl-carbonyl)-amino group,” and those groupsin which R^(a5) is a heterocyclic group are referred to as“bis(heterocyclic ring-oxy-carbonyl-carbonyl)-amino group.”

Among the groups represented by the formula (ω-5E), those groups inwhich R^(a5) is a hydrocarbon group are referred to as“bis(hydrocarbon-sulfanyl-carbonyl)-amino group,” and those groups inwhich R^(a5) is a heterocyclic group are referred to as“bis(heterocyclic ring-sulfanyl-carbonyl)-amino group.”

Among the groups represented by the formula (ω-6E), those groups inwhich R^(a5) is a hydrocarbon group are referred to as“bis(hydrocarbon-thiocarbonyl)-amino group,” and those groups in whichR^(a5) is a heterocyclic group are referred to as “bis(heterocyclicring-thiocarbonyl)-amino group.”

Among the groups represented by the formula (ω-7E), those groups inwhich R^(a5) is a hydrocarbon group are referred to as“bis(hydrocarbon-oxy-thiocarbonyl)-amino group,” and those groups inwhich R^(a5) is a heterocyclic group are referred to as“bis(heterocyclic ring-oxy-thiocarbonyl)-amino group.”

Among the groups represented by the formula (ω-8E), those groups inwhich R^(a5) is a hydrocarbon group are referred to as“bis(hydrocarbon-sulfanyl-thiocarbonyl)-amino group,” and those groupsin which R^(a5) is a heterocyclic group are referred to as“bis(heterocyclic ring-sulfanyl-thiocarbonyl)-amino group.”

Among the groups represented by the formula (ω-9E), those groups inwhich R^(a5) is a hydrocarbon group are referred to as“bis(N-hydrocarbon-carbamoyl)-amino group,” and those groups in whichR^(a5) is a heterocyclic group are referred to as “bis(N-heterocyclicring-carbamoyl)-amino group.”

Among the groups represented by the formula (ω-10E), those groups inwhich both R^(a5) and R^(b5) are hydrocarbon groups are referred to as“bis[N,N-di(hydrocarbon)-carbamoyl]-amino group,” those groups in whichboth R^(a5) and R^(b5) are heterocyclic groups are referred to as“bis[N,N-di(heterocyclic ring)-carbamoyl]-amino group,” groups in whichR^(a5) is a hydrocarbon group and R^(b5) is a heterocyclic group arereferred to as “bis(N-hydrocarbon-N-heterocyclic ring-carbamoyl)-aminogroup,” and those groups in which R^(a5) and R^(b5) combine to eachother, together with the nitrogen atom to which they bind, to form acyclic amino groups are referred to as “bis(cyclic amino-carbonyl)aminogroup.”

Among the groups represented by the formula (ω-11E), those groups inwhich R^(a5) is a hydrocarbon group are referred to as“bis(N-hydrocarbon-thiocarbamoyl)-amino group,” and those groups inwhich R^(a5) is a heterocyclic group are referred to as“bis(N-heterocyclic ring-thiocarbamoyl)-amino group.”

Among the groups represented by the formula (ω-12E), those groups inwhich both R^(a5) and R^(b5) are hydrocarbon groups are referred to as“bis[N,N-di(hydrocarbon)-thiocarbamoyl]-amino group,” those groups inwhich both R^(a5) and R^(b5) are heterocyclic groups are referred to as“bis[N,N-di(heterocyclic ring)-thiocarbamoyl]-amino group,” those groupsin which R^(a5) is a hydrocarbon group and R^(b5) is a heterocyclicgroup are referred to as “bis(N-hydrocarbon-N-heterocyclicring-thiocarbamoyl)-amino group,” and those groups in which R^(a5) andR^(b5) combine to each other, together with the nitrogen atom to whichthey bind, to form a cyclic amino group are referred to as “bis(cyclicamino-thiocarbonyl)-amino group.”

Among the groups represented by the formula (ω-13E), those groups inwhich R^(a5) is a hydrocarbon group are referred to as“bis(N-hydrocarbon-sulfamoyl)-amino group,” and those groups in whichR^(a5) is a heterocyclic group are referred to as “bis(N-heterocyclicring-sulfamoyl)-amino group.”

Among the groups represented by the formula (ω-14E), those groups inwhich both R^(a5) and R^(b5) are hydrocarbon groups are referred to as“bis[N,N-di(hydrocarbon)-sulfamoyl]-amino group,” those groups in whichboth R^(a5) and R^(b5) are heterocyclic groups are referred to as“bis[N,N-di(heterocyclic ring)-sulfamoyl]-amino group,” those groups inwhich R^(a5) is a hydrocarbon group and R^(b5) is a heterocyclic groupare referred to as “bis(N-hydrocarbon-N-heterocyclicring-sulfamoyl)-amino group,” and those groups in which R^(a5) andR^(b5) combine to each other, together with the nitrogen atom to whichthey bind, to form a cyclic amino group are referred to as “bis(cyclicamino-sulfonyl)amino group.”

Among the groups represented by the formula (ω-15E), those groups inwhich R^(a5) is a hydrocarbon group are referred to as“bis(N-hydrocarbon-sulfinamoyl)-amino group,” and those groups in whichR^(a5) is a heterocyclic group are referred to as “bis(N-heterocyclicring-sulfinamoyl)-amino group.”

Among the groups represented by the formula (ω-16E), those groups inwhich R^(a5) and R^(b5) are hydrocarbon groups are referred to as“bis[N,N-di(hydrocarbon)-sulfinamoyl]-amino group,” those groups inwhich R^(a5) and R^(b5) are heterocyclic groups are referred to as“bis[N,N-di(heterocyclic ring)-sulfinamoyl]-amino group,” those groupsin which R^(a5) is a hydrocarbon group and R^(b5) is a heterocyclicgroup are referred to as “bis(N-hydrocarbon-N-heterocyclicring-sulfinamoyl)-amino group,” and those groups in which R^(a5) andR^(b5) combine to each other, together with the nitrogen atom to whichthey bind, to form a cyclic amino group are referred to as “bis(cyclicamino-sulfinyl)amino group.”

Among the groups represented by the formula (ω-17E), those groups inwhich R^(a5) is a hydrocarbon group are referred to as“bis(hydrocarbon-oxy-sulfonyl)-amino group,” and those groups in whichR^(a5) is a heterocyclic group are referred to as “bis(heterocyclicring-oxy-sulfonyl)-amino group.”

Among the groups represented by the formula (ω-18E), those groups inwhich R^(a5) is a hydrocarbon group are referred to as“bis(hydrocarbon-oxy-sulfinyl)-amino group,” and those groups in whichR^(a5) is a heterocyclic group are referred to as “bis(heterocyclicring-oxy-sulfinyl)-amino group.”

Among the groups represented by the formula (ω-19E), those groups inwhich both R^(a5) and R^(b5) are hydrocarbon groups are referred to as“bis[O,O′-di(hydrocarbon)-phosphono]-amino group,” those groups in whichboth R^(a5) and R^(b5) are heterocyclic groups are referred to as“bis[O,O′-di(heterocyclic ring)-phosphono]-amino group,” and thosegroups in which R^(a5) is a hydrocarbon group and R^(b5) is aheterocyclic group are referred to as “bis(O-hydrocarbon-O′-heterocyclicring-phosphono)-amino group.”

Among the groups represented by the formula (ω-20E), those groups inwhich R^(a5) is a hydrocarbon group are referred to as“bis(hydrocarbon-sulfonyl)-amino group,” and those groups in whichR^(a5) is a heterocyclic group are referred to as “bis( heterocyclicring-sulfonyl)-amino group.”

Among the groups represented by the formula (ω-21E), those groups inwhich R^(a5) is a hydrocarbon group are referred to as“bis(hydrocarbon-sulfinyl)-amino group,” and those groups in whichR^(a5) is a heterocyclic group are referred to as “bis(heterocyclicring-sulfinyl)-amino group.”

Examples of the hydrocarbon in the groups represented by theaforementioned formulas (ω-1E) through (ω-21E) include the similargroups to the aforementioned hydrocarbon group. Examples of thebis(hydrocarbon-carbonyl)-amino groups represented by the formula (ω-1E)include, for example, a bis(alkyl-carbonyl)-amino group, abis(alkenyl-carbonyl)-amino group, a bis(alkynyl-carbonyl)-amino group,a bis(cycloalkyl-carbonyl)-amino group, abis(cycloalkenyl-carbonyl)-amino group, abis(cycloalkanedienyl-carbonyl)-amino group, abis(cycloalkyl-alkyl-carbonyl)-amino group which are bis(aliphatichydrocarbon-carbonyl)-amino groups; a bis(aryl-carbonyl)-amino group; abis(aralkyl-carbonyl)-amino group; a bis(bridged cyclichydrocarbon-carbonyl)-amino group; a bis(spiro cyclichydrocarbon-carbonyl)-amino group; and a bis(terpene familyhydrocarbon-carbonyl)-amino group. In the following descriptions, groupsrepresented by the formulas (ω-2E) through (ω-21E) are similar to thoseexplained above.

Examples of the heterocyclic ring in the groups represented by theaforementioned formulas (ω-1E) through (ω-21E) include similar groups tothe aforementioned heterocyclic group. Examples of the bis(heterocyclicring-carbonyl)-amino group represented by the formula (ω-1E) include,for example, a bis(monocyclic heteroaryl-carbonyl)-amino group, abis(fused polycyclic heteroaryl-carbonyl)-amino group, a bis(monocyclicnon-aromatic heterocyclic-carbonyl)-amino group, and a bis(fusedpolycyclic non-aromatic heterocyclic-carbonyl)-amino group. In thefollowing descriptions, groups represented by the formulas (ω-2E)through (ω-21E) are similar to those groups explained above.

Examples of the cyclic amino in the groups represented by theaforementioned formulas (ω-1E) through (ω-16E) include similar groups tothe aforementioned cyclic amino group.

The aforementioned acyl-amino group and di(acyl)-amino group aregenerically referred to as “acyl substituted amino group.” Furthermore,the aforementioned N-hydrocarbon-amino group, N,N-di(hydrocarbon)-aminogroup, N-heterocyclic-amino group, N-hydrocarbon-N-heterocyclic-aminogroup, cyclic amino group, acyl-amino group, and di(acyl)-amino groupare generically referred to as “substituted amino group.” Furthermore,these substituted amino group and amino group are generically referredto as “amino group which may be substituted.”

In the following descriptions, compounds represented by theaforementioned general formula (I) are explained in details.

Examples of the “acyl group” in the definition of A include similargroups to the “acyl group” in the aforementioned definition.

A represents hydrogen atom or an acyl group. Hydrogen atom,“hydrocarbon-carbonyl group,” and “hydrocarbon-sulfonyl group” arepreferred, and hydrogen atom, acetyl group, and para-toluenesulfonylgroup are more preferred.

X represents oxygen atom or NH.

One of R¹ and R² represents hydrogen atom and the other represents theformula —X-A. The compounds wherein R¹ is the formula —X-A and R² ishydrogen atom are preferred. The compounds wherein R¹ is the formula—O-A and R² is hydrogen atom are more preferred, and the compoundswherein A is hydrogen atom, acetyl group or para-toluenesulfonyl groupare particularly preferred.

Y represents a sulfonyl group (—SO₂—) or a carbonyl group (—CO—).Sulfonyl group is preferred.

Examples of the “cyclic group” of “cyclic group which may besubstituted” in the definition of R⁵ include similar groups to the“cyclic group” in the aforementioned definition. Aromatic ring group,and cycloalkyl group are preferred, and phenyl group, naphthyl group,furyl group, pyridyl group, benzimidazolyl group, and cyclohexyl groupare more preferred, and phenyl group is most preferred.

Examples of the “substituent” in the definition of “cyclic group whichmay be substituted” in the definition of R⁵ include similar groups tothe “substituent” explained for the aforementioned definition “which maybe substituted.” Halogen atom such as chlorine atom and fluorine atom;nitro group; alkyl group such as methyl group and tert-butyl group;halogenated alkyl group such as trifluoromethyl group; hydroxy group;alkoxy group such as methoxy group; alkylenedioxy group such asmethylenedioxy group; amino group; N,N-di(hydrocarbon)-amino group suchas dimethylamino group; and hydrocarbon-sulfonyl group such asmethanesulfonyl group are preferred.

R⁵ represents a cyclic group which may be substituted. Phenyl group,2,6-difluorophenyl group, 2,4-dichlorophenyl group, 3-nitrophenyl group,4-nitrophenyl group, 2-methylphenyl group, 4-(tert-butyl)phenyl group,2-(trifluoromethyl)phenyl group, 4-(trifluoromethyl)phenyl group,3,4-dihydroxyphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group,2,3-dimethoxyphenyl group, 3,5-dimethoxyphenyl group,3,4-methylenedioxyphenyl group, 3-aminophenyl group,4-(dimethylamino)phenyl group, 4-methanesulfonylphenyl group, 1-naphthylgroup, 5-methylfuran-2-yl group, pyridin-2-yl group, benzimidazol-2-ylgroup, and cyclohexyl group are preferred, and phenyl group,4-(tert-butyl)phenyl group, and 2,3-dimethoxyphenyl group are morepreferred.

Examples of the “substituent” in the definition of “C₁ to C₄ alkylenegroup which may be substituted” in the definition of Z include similargroups to the “substituent” explained for the aforementioned definition“which may be substituted.”

Examples of the “C₁ to C₄ alkylene group” of “C₁ to C₄ alkylene groupwhich may be substituted” in the definition of Z include straight chainor branched chain C₁ to C₄ alkylene groups such as methylene group,ethylene group, ethane-1,1-diyl group, propane-1,3-diyl group,propane-1,2-diyl group, propane-2,2-diyl group, or butane-1,4-diylgroup.

Z represents a single bond or a C₁ to C₄ alkylene group which may besubstituted. A single bond, methylene group, ethylene group, andethane-1,1-diyl group are preferred, and methylene group is morepreferred.

When Z is substituted, said substituent may bind to R⁵ to form a cyclicgroup. Specific examples of these compounds include, for example, thecompounds wherein the formula -Z-R⁵ is1,2,3,4-tetrahydroisoquinolin-2-yl group or the like.

Examples of the “substituent” in the definition of “C₁ to C₆ alkyl groupwhich may be substituted” in the definition of R⁶ include similar groupsto the “substituent” explained for the aforementioned definition “whichmay be substituted.”

Examples of the “C₁ to C₆ alkyl group” of “C₁ to C₆ alkyl group whichmay be substituted” in the definition of R⁶ include a straight chain ora branched chain C₁ to C₆ alkyl group such as methyl group, ethyl group,n-propyl group, isopropyl group, n-butyl group, isobutyl group,sec-butyl group, tert-butyl group, n-pentyl group, n-hexyl group and thelike.

R⁶ represents hydrogen atom or a C₁ to C₆ alkyl group which may besubstituted. Hydrogen atom and methyl group are preferred, and hydrogenatom is more preferred.

R⁶ may bind to Z or R⁵ to form a cyclic group. Specific examples ofthese compounds include, for example, the compounds wherein thefollowing formula:

is 1,2,3,4-tetrahydroisoquinolin-2-yl group, 3-phenylpiperidin-1-ylgroup or the like.

One of R³ and R⁴ represents hydrogen atom and the other represents thefollowing formula.

The compounds wherein R³ is the following formula:

and R⁴ is hydrogen atom;wherein R³ is hydrogen atom and R⁴ is the following formula;

and wherein R³ is the following formula:

and R⁴ is hydrogen atom are preferred.The compounds wherein R³ is the following formula:

and R⁴ is hydrogen atom; andwherein R³ is hydrogen atom and R⁴ is the following formula:

are more preferred.

The following compounds are preferred as the compound represented by thegeneral formula (I). The compound numbers correspond to those in thetable shown below.

-   -   N-Benzyl-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-1);    -   N-(2,6-Difluorobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-2);    -   N-(2,4-Dichlorobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-3);    -   N-(3-Nitrobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-4);    -   N-(4-Nitrobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-5);    -   N-(2-Methylbenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-6);    -   N-[4-(tert-Butyl)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-7);    -   N-[2-(Trifluoromethyl)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-8);    -   N-[4-(Trifluoromethyl)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-9);    -   N-(3,4-Dihydroxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-10);    -   N-(2-Methoxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-11);    -   N-(3-Methoxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-12);    -   N-(2,3-Dimethoxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-13);    -   N-(3,5-Dimethoxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-14);    -   N-(3,4-Methylenedioxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-15);    -   N-(3-Aminobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-16);    -   N-[4-(Dimethylamino)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-17);    -   N-[4-(Methanesulfonyl)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-18);    -   N-(1-Naphthylmethyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-19);    -   N-[(5-Methylfuran-2-yl)methyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-20);    -   N-[(Pyridin-2-yl)methyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-21);    -   N-[(Benzimidazol-2-yl)methyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-22);    -   N-Cyclohexylmethyl-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-23);    -   N-Phenyl-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-24);    -   N-(2-Phenethyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-25);    -   N-(1-Phenethyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-26);    -   N-Benzyl-N-methyl-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide        (Compound No. 1-27);    -   N-Benzyl-5-hydroxynaphthalene-1-sulfonamide (Compound No. 2-1);    -   N-(2,6-Difluorobenzyl)-5-hydroxynaphthalene-1-sulfonamide        (Compound No. 2-2);    -   N-(2,4-Dichlorobenzyl)-5-hydroxynaphthalene-1-sulfonamide        (Compound No. 2-3);    -   N-(3-Nitrobenzyl)-5-hydroxynaphthalene-1-sulfonamide (Compound        No. 2-4);    -   N-(4-Nitrobenzyl)-5-hydroxynaphthalene-1-sulfonamide (Compound        No. 2-5);    -   N-(2-Methylbenzyl)-5-hydroxynaphthalene-1-sulfonamide (Compound        No. 2-6);    -   N-[4-(tert-Butyl)benzyl]-5-hydroxynaphthalene-i-sulfonamide        (Compound No. 2-7);    -   N-[2-(Trifluoromethyl)benzyl]-5-hydroxynaphthalene-1-sulfonamide        (Compound No. 2-8);    -   N-[4-(Trifluoromethyl)benzyl]-5-hydroxynaphthalene-1-sulfonamide        (Compound No. 2-9);    -   N-(3,4-Dihydroxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide        (Compound No. 2-10);    -   N-(2-Methoxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide        (Compound No. 2-11);    -   N-(3-Methoxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide        (Compound No. 2-12);    -   N-(2,3-Dimethoxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide        (Compound No. 2-13);    -   N-(3,5-Dimethoxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide        (Compound No. 2-14);    -   N-(3,4-Methylenedioxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide        (Compound No. 2-15);    -   N-(3-Aminobenzyl)-5-hydroxynaphthalene-1-sulfonamide (Compound        No. 2-16);    -   N-[4-(Dimethylamino)benzyl]-5-hydroxynaphthalene-1-sulfonamide        (Compound No. 2-17);    -   N-[4-(Methanesulfonyl)benzyl]-5-hydroxynaphthalene-1-sulfonamide        (Compound No. 2-18);    -   N-(1-Naphthylmethyl)-5-hydroxynaphthalene-1-sulfonamide        (Compound No. 2-19);    -   N-[(5-Methylfuran-2-yl)methyl]-5-hydroxynaphthalene-1-sulfonamide        (Compound No. 2-20);    -   N-[(Pyridin-2-yl)methyl]-5-hydroxynaphthalene-1-sulfonamide        (Compound No. 2-21);    -   N-[(Benzimidazol-2-yl)methyl]-5-hydroxynaphthalene-1-sulfonamide        (Compound No. 2-22);    -   N-Cyclohexylmethyl-5-hydroxynaphthalene-1-sulfonamide (Compound        No. 2-23);    -   N-Phenyl-5-hydroxynaphthalene-1-sulfonamide (Compound No. 2-24);    -   N-(2-Phenethyl)-5-hydroxynaphthalene-1-sulfonamide (Compound No.        2-25);    -   N-(1-Phenethyl)-5-hydroxynaphthalene-1-sulfonamide (Compound No.        2-26);    -   N-Benzyl-N-methyl-5-hydroxynaphthalene-1-sulfonamide (Compound        No. 2-27);    -   5-Acetyloxy-N-benzylnaphthalene-2-sulfonamide (Compound No.        3-1);    -   5-Acetyloxy-N-(2,4-dichlorobenzyl)naphthalene-2-sulfonamide        (Compound No. 3-2);    -   5-Acetyloxy-N-(3-nitrobenzyl)naphthalene-2-sulfonamide (Compound        No. 3-3);    -   5-Acetyloxy-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide        (Compound No. 3-4);    -   5-Acetyloxy-N-[4-(trifluoromethyl)benzyl]naphthalene-2-sulfonamide        (Compound No. 3-5);    -   5-Acetyloxy-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide        (Compound No. 3-6);    -   5-Acetyloxy-N-(3-aminobenzyl)naphthalene-2-sulfonamide (Compound        No. 3-7);    -   5-Acetyloxy-N-(1-naphthylmethyl)naphthalene-2-sulfonamide        (Compound No. 3-8);    -   5-Acetyloxy-N-[(5-methylfuran-2-yl)methyl]naphthalene-2-sulfonamide        (Compound No. 3-9);    -   5-Acetyloxy-N-[(pyridin-2-yl)methyl]naphthalene-2-sulfonamide        (Compound No. 3-10);    -   5-Acetyloxy-N-(cyclohexylmethyl)naphthalene-2-sulfonamide        (Compound No. 3-11);    -   5-Acetyloxy-N-phenylnaphthalene-2-sulfonamide (Compound No.        3-12);    -   5-Acetyloxy-N-(2-phenethyl)naphthalene-2-sulfonamide (Compound        No. 3-13);    -   5-Acetyloxy-N-(1-phenethyl)naphthalene-2-sulfonamide (Compound        No. 3-14);    -   5-Acetyloxy-N-benzyl-N-methylnaphthalene-2-sulfonamide (Compound        No. 3-15);    -   N-Benzyl-5-hydroxynaphthalene-2-sulfonamide (Compound No. 4-1);    -   N-(2,4-Dichlorobenzyl)-5-hydroxynaphthalene-2-sulfonamide        (Compound No. 4-2);    -   N-(3-Nitrobenzyl)-5-hydroxynaphthalene-2-sulfonamide (Compound        No. 4-3);    -   N-[4-(tert-Butyl)benzyl]-5-hydroxynaphthalene-2-sulfonamide        (Compound No. 4-4);    -   N-[4-(Trifluoromethyl)benzyl]-5-hydroxynaphthalene-2-sulfonamide        (Compound No. 4-5);    -   N-(2,3-Dimethoxybenzyl)-5-hydroxynaphthalene-2-sulfonamide        (Compound No. 4-6);    -   N-(3-Aminobenzyl)-5-hydroxynaphthalene-2-sulfonamide (Compound        No. 4-7);    -   N-(1-Naphthylmethyl)-5-hydroxynaphthalene-2-sulfonamide        (Compound No. 4-8);    -   N-[(5-Methylfuran-2-yl)methyl]-5-hydroxynaphthalene-2-sulfonamide        (Compound No. 4-9);    -   N-[(Pyridin-2-yl)methyl]-5-hydroxynaphthalene-2-sulfonamide        (Compound No. 4-10);    -   N-(Cyclohexylmethyl)-5-hydroxynaphthalene-2-sulfonamide        (Compound No. 4-11);    -   N-Phenyl-5-hydroxynaphthalene-2-sulfonamide (Compound No. 4-12);    -   N-(2-Phenethyl)-5-hydroxynaphthalene-2-sulfonamide (Compound No.        4-13);    -   N-(1-Phenethyl)-5-hydroxynaphthalene-2-sulfonamide (Compound No.        4-14);    -   N-Benzyl-N-methyl-5-hydroxynaphthalene-2-sulfonamide (Compound        No. 4-15);    -   5-Acetylamino-N-benzylnaphthalene-2-sulfonamide (Compound No.        5-1);    -   5-Acetylamino-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide        (Compound No. 5-2);    -   5-Acetylamino-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide        (Compound No. 5-3);    -   5-Acetylamino-N-benzyl-N-methylnaphthalene-2-sulfonamide        (Compound No. 5-4);    -   5-Amino-N-benzylnaphthalene-2-sulfonamide (Compound No. 6-1;        This compound is represented as a hydrochloride in the following        examples.);    -   5-Amino-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide        (Compound No. 6-2; This compound is represented as a        hydrochloride in the following examples.);    -   5-Amino-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide        (Compound No. 6-3; This compound is represented as a        hydrochloride in the following examples.);    -   5-Amino-N-benzyl-N-methylnaphthalene-2-sulfonamide (Compound No.        6-4; This compound is represented as a hydrochloride in the        following examples.);    -   6-Acetylamino-N-benzylnaphthalene-1-sulfonamide (Compound No.        7-1);    -   6-Acetylamino-N-[4-(tert-butyl)benzyl]naphthalene-1-sulfonamide        (Compound No. 7-2);    -   6-Acetylamino-N-(2,3-dimethoxybenzyl)naphthalene-1-sulfonamide        (Compound No. 7-3);    -   6-Amino-N-benzylnaphthalene-1-sulfonamide (Compound No. 8-1;        This compound is represented as a hydrochloride in the following        examples.);    -   6-Amino-N-[4-(tert-butyl)benzyl]naphthalene-1-sulfonamide        (Compound No. 8-2; This compound is represented as a        hydrochloride in the following examples.);    -   6-Amino-N-(2,3-dimethoxybenzyl)naphthalene-1-sulfonamide        (Compound No. 8-3; This compound is represented as a        hydrochloride in the following examples.);    -   6-Acetylamino-N-benzylnaphthalene-2-sulfonamide (Compound No.        9-1);    -   6-Acetylamino-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide        (Compound No. 9-2);    -   6-Acetylamino-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide        (Compound No. 9-3);    -   6-Amino-N-benzylnaphthalene-2-sulfonamide (Compound No. 10-1;        This compound is represented as a hydrochloride in the following        examples.);    -   6-Amino-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide        (Compound No. 10-2; This compound is represented as a        hydrochloride in the following examples.);    -   6-Amino-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide        (Compound No. 10-3; This compound is represented as a        hydrochloride in the following examples.);    -   5-Amino-N-benzylnaphthalene-1-carboxamide (Compound No. 11-1);    -   5-Amino-N-[4-(tert-butyl)benzyl]naphthalene-1-carboxamide        (Compound No. 11-2);    -   5-Amino-N-(2,3-dimethoxybenzyl)naphthalene-1-carboxamide        (Compound No. 11-3).

The compounds represented by the general formula (I) may form salts.Kinds of salts are not particularly limited. When acidic groups exist,examples include metal salts such as lithium salt, sodium salt,potassium salt, magnesium salt, and calcium salt; or ammonium salts suchas ammonium salt, methylammonium salt, dimethylammonium salt,trimethylammonium salt, and dicyclohexylammonium salt, and when basicgroups exist, examples include mineral acid salts such as hydrochloride,hydrobromide, sulfate, nitrate, and phosphate, or organic acid saltssuch as methane sulfonate, benzene sulfonate, para-toluene sulfonate,acetate, propionate, tartrate, fumarate, maleate, malate, oxalate,succinate, citrate, benzoate, mandelate, cinnamate, and lactate. Saltsmay sometimes be formed with amino acids such as glycine. As activeingredients of the medicaments of the present invention,pharmacologically acceptable salts are suitable.

The compounds or salts thereof represented by the general formula (I)may exist as hydrates or solvates. Furthermore, the compoundsrepresented by the general formula (I) may sometimes have one or moreasymmetric carbons, and may exist as stereoisomers such as opticallyactive isomers and diastereomers. As active ingredients of themedicaments of the present invention, a pure form of a stereoisomer, anymixture of enantiomers or diastereomers, a racemate or the like may beused.

Furthermore, when the compounds represented by the general formula (I)have an olefinic double bond, its configuration may be in either E or Z.As an active ingredient of the medicament of the present invention, ageometrical isomer in either of the configurations or a mixture thereofmay be used.

Examples of the compounds encompassed within the general formula (I),which are for active ingredients of the medicaments of the presentinvention, are shown below. However, the active ingredients of themedicaments of the present invention are not limited to the followingcompounds.

The abbreviations used in the following tables have the followingmeanings.

Me: methyl group.

Compound Number Z R⁵ R⁶ 1-1 —CH₂— phenyl H 1-2 —CH₂— 2,6-difluorophenylH 1-3 —CH₂— 2,4-dichiorophenyl H 1-4 —CH₂— 3-nitrophenyl H 1-5 —CH₂—4-nitrophenyl H 1-6 —CH₂— 2-methylphenyl H 1-7 —CH₂—4-(tert-butyl)phenyl H 1-8 —CH₂— 2-(trifluoromethyl)phenyl H 1-9 —CH₂—4-(trifluoromethyl)phenyl H 1-10 —CH₂— 3,4-dihydroxyphenyl H 1-11 —CH₂—2-methoxyphenyl H 1-12 —CH₂— 3-methoxyphenyl H 1-13 —CH₂—2,3-dimethoxyphenyl H 1-14 —CH₂— 3,5-dimethoxyphenyl H 1-15 —CH₂—3,4-methylenedioxyphenyl H 1-16 —CH₂— 3-aminophenyl H 1-17 —CH₂—4-(dimethylamino)phenyl H 1-18 —CH₂— 4-methanesulfonylphenyl H 1-19—CH₂— 1-naphthyl H 1-20 —CH₂— 5-methylfuran-2-yl H 1-21 —CH₂—Pyridin-2-yl H 1-22 —CH₂— Benzimidazol-2-yl H 1-23 —CH₂— cyclohexyl H1-24 single bond phenyl H 1-25 —CH₂CH₂— phenyl H 1-26 —CH(CH₃)— phenyl H1-27 —CH₂— phenyl Me

Compound Number Z R⁵ R⁶ 2-1 —CH₂— phenyl H 2-2 —CH₂— 2,6-difluorophenylH 2-3 —CH₂— 2,4-dichlorophenyl H 2-4 —CH₂— 3-nitrophenyl H 2-5 —CH₂—4-nitrophenyl H 2-6 —CH₂— 2-methyiphenyl H 2-7 —CH₂—4-(tert-butyl)phenyl H 2-8 —CH₂— 2-(trifluoromethyl)phenyl H 2-9 —CH₂—4-(trifluoromethyl)phenyl H 2-10 —CH₂— 3,4-dihydroxyphenyl H 2-11 —CH₂—2-methoxyphenyl H 2-12 —CH₂— 3-methoxyphenyl H 2-13 —CH₂—2,3-dimethoxyphenyl H 2-14 —CH₂— 3,5-dimethoxyphenyl H 2-15 —CH₂—3,4-methylenedioxyphenyl H 2-16 —CH₂— 3-aminophenyl H 2-17 —CH₂—4-(dimethylamino)phenyl H 2-18 —CH₂— 4-methanesulfonylphenyl H 2-19—CH₂— 1-naphthyl H 2-20 —CH₂— 5-methylfuran-2-yl H 2-21 —CH₂—Pyridin-2-yl H 2-22 —CH₂— Benzimidazol-2-yl H 2-23 —CH₂— cyclohexyl H2-24 single bond phenyl H 2-25 —CH₂CH₂— phenyl H 2-26 —CH(CH₃)— phenyl H2-27 —CH₂— phenyl Me

Compound Number Z R⁵ R⁶ 3-1 —CH₂— phenyl H 3-2 —CH₂— 2,4-dichlorophenylH 3-3 —CH₂— 3-nitrophenyl H 3-4 —CH₂— 4-(tert-butyl)phenyl H 3-5 —CH₂—4-(trifluoromethyl)phenyl H 3-6 —CH₂— 2,3-dimethoxyphenyl H 3-7 —CH₂—3-aminophenyl H 3-8 —CH₂— 1-naphthyl H 3-9 —CH₂— 5-methylfuran-2-yl H3-10 —CH₂— Pyridin-2-yl H 3-11 —CH₂— cyclohexyl H 3-12 single bondphenyl H 3-13 —CH₂CH₂— phenyl H 3-14 —CH(CH₃)— phenyl H 3-15 —CH₂—phenyl Me

Compound Number Z R⁵ R⁶ 4-1 —CH₂— phenyl H 4-2 —CH₂— 2,4-dichlorophenylH 4-3 —CH₂— 3-nitrophenyl H 4-4 —CH₂— 4-(tert-butyl)phenyl H 4-5 —CH₂—4-(trifluoromethyl)phenyl H 4-6 —CH₂— 2,3-dimethoxyphenyl H 4-7 —CH₂—3-aminophenyl H 4-8 —CH₂— 1-naphthyl H 4-9 —CH₂— 5-methylfuran-2-yl H4-10 —CH₂— Pyridin-2-yl H 4-11 —CH₂— cyclohexyl H 4-12 single bondphenyl H 4-13 —CH₂CH₂— phenyl H 4-14 —CH(CH₃)— phenyl H 4-15 —CH₂—phenyl Me

Compound Number Z R⁵ R⁶ 5-1 —CH₂— phenyl H 5-2 —CH₂—4-(tert-butyl)phenyl H 5-3 —CH₂— 2,3-dimethoxyphenyl H 5-4 —CH₂— phenylMe

Compound Number Z R⁵ R⁶ 6-1 —CH₂— phenyl H 6-2 —CH₂—4-(tert-butyl)phenyl H 6-3 —CH₂— 2,3-dimethoxyphenyl H 6-4 —CH₂— phenylMe

Compound Number Z R⁵ R⁶ 7-1 —CH₂— phenyl H 7-2 —CH₂—4-(tert-butyl)phenyl H 7-3 —CH₂— 2,3-dimethoxyphenyl H

Compound Number Z R⁵ R⁶ 8-1 —CH₂— phenyl H 8-2 —CH₂—4-(tert-butyl)phenyl H 8-3 —CH₂— 2,3-dimethoxyphenyl H

Compound Number Z R⁵ R⁶ 9-1 —CH₂— phenyl H 9-2 —CH₂—4-(tert-butyl)phenyl H 9-3 —CH₂— 2,3-dimethoxyphenyl H

Compound Number Z R⁵ R⁶ 10-1 —CH₂— phenyl H 10-2 —CH₂—4-(tert-butyl)phenyl H 10-3 —CH₂— 2,3-dimethoxyphenyl H

Compound Number Z R⁵ R⁶ 11-1 —CH₂— phenyl H 11-2 —CH₂—4-(tert-butyl)phenyl H 11-3 —CH₂— 2,3-dimethoxyphenyl H

The compounds represented by the general formula (I) of the presentinvention can be prepared, for example, by methods shown below.

<<Preparation Method 1>>

In the compounds represented by the general formula (I) of the presentinvention, the compounds wherein R¹ is a group represented by theformula —O-A wherein A represents hydrogen atom or an acyl group, R² ishydrogen atom, R³ is a group represented by the following formula:

wherein R⁵ represents a cyclic group which may be substituted, Zrepresents a single bond or a C₁ to C₄ alkylene group which may besubstituted; or when Z is substituted, said substituent may bind to R⁵to form a cyclic group, R⁶ represents hydrogen atom or a C₁ to C₆ alkylgroup which may be substituted; or R⁶ may bind to Z or R⁵ to form acyclic group, R⁴ is hydrogen atom can be prepared, for example, by amethod described in the reaction scheme 1.

5-{[(4-Methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonyl chloride (1) canbe prepared, for example, by the method disclosed in the U.S. Pat. No.5,378,715. As for the amine (2) wherein R⁵, R⁶, and Z have the samemeanings as those defined in the general formula (I), most of the aminesin the free form or acid addition salts are widely available in themarket, and commercial products can be obtained and directly used.Furthermore, the amine (2) wherein R⁵, R⁶, and Z have the same meaningsas those defined in the general formula (I) can also prepared by methodsreadily understandable by those skilled in the art (for example,reduction of a corresponding nitro compound, reduction of a cyanocompound, reduction of a carbamoyl compound and the like), and it isalso understandable that the resulting amine can be used for preparationof the compounds of the present invention.

By reacting 5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonylchloride (1) with the amine (2) wherein R⁵, R⁶, and Z have the samemeanings as those defined in the general formula (I), the compound ofthe formula (3) wherein R⁵, R⁶, and Z have the same meanings as thosedefined in the general formula (I) can be obtained. The compound of theformula (3) is encompassed within the general formula (I). This reactionis carried out in the presence or absence of a base and/or a catalyst,with or without a solvent, at a reaction temperature of from −30° C. toa refluxing temperature of a solvent (at a reaction temperature of from−30° C. to 150° C., when the reaction is carried out without a solvent).

Examples of the bases include inorganic bases such as sodium hydroxide,potassium hydroxide, sodium carbonate, potassium carbonate, and sodiumhydrogencarbonate; and organic bases such as pyridine, triethylamine,ethyldiisopropylamine, and N,N-diethylaniline. Examples of the catalystsinclude 4-dimethylaminopyridine and tetrabutylammonium bromide. Anysolvent can be used as long as it does not inhibit the reaction, andexamples include esters such as ethyl formate, methyl acetate, ethylacetate, and butyl acetate; halides such as dichloromethane,dichloroethane, and chloroform; ethers such as tetrahydrofuran,1,2-dimethoxyethane, and 1,4-dioxane; substituted or unsubstitutedbenzenes such as benzene, toluene, monochlorobenzene, and1,2-dichlorobenzene; amides such as N,N-dimethylformamide andN-methylpyrrolidone; alcohols such as methanol, ethanol, 1-propanol, and2-propanol; ketones such as acetone and methyl ethyl ketone; and water.These solvents can be used alone or as a mixture, or as two phasesolvents.

The tosyl group of the resulting compound of the formula (3) wherein R⁵,R⁶, and Z have the same meanings as those defined in the general formula(I) is then hydrolyzed to prepare the compounds represented by theformula (4). The compound of the formula (4) is encompassed within thegeneral formula (I). This reaction is carried out in the presence of anacid or a base, with or without a solvent, at a reaction temperature offrom 0° C. to a refluxing temperature of a solvent (at a reactiontemperature of from 0° C. to 150° C., when the reaction is carried outwithout a solvent).

Examples of the acids include mineral acids such as hydrochloric acidand sulfuric acid; organic acids such as formic acid, acetic acid,methanesulfonic acid, and p-toluenesulfonic acid; and Lewis acids suchas alminium chloride and triethyloxonium tetrafluoroborate. Examples ofthe bases include inorganic bases such as sodium hydroxide, potassiumhydroxide, potassium carbonate, and sodium hydrogencarbonate; andorganic bases such as hydrazine. Any solvent can be used as long as itdoes not inhibit the reaction, and examples include ethers such astetrahydrofuran, 1,2-dimethoxyethane, and 1,4-dioxane; alcohols such asmethanol, ethanol, 1-propanol, and 2-propanol; and water. These solventscan be used alone or as a mixture, or as two phase solvents.

The compound of the formula (4) wherein R⁵, R⁶, and Z have the samemeanings as those defined in the general formula (I) is then reactedwith the acylating agent (5) wherein A represents an acyl group, Wrepresents halogen atom; acyloxy group such as acetoxy group, benzoyloxygroup, methanesulfonyl group, and tosyl group; imidoxy group such as(2,5-dioxopyrrolidin-1-yl group; 1-imidazolyl group; and hydroxy group,to prepare the compounds represented by the formula (6), which areencompassed within the general formula (I), wherein A, R⁵, R⁶, and Zhave the same meanings as those defined in the general formula (I). Thisreaction is carried out in the presence or absence of a base and/or anadjuvant for acylation, with or without a solvent, at a reactiontemperature of from −30° C. to a refluxing temperature of a solvent (ata reaction temperature of from −30° C. to 150° C., when the reaction iscarried out without a solvent).

Examples of the bases include inorganic bases such as sodium hydroxide,potassium hydroxide, sodium carbonate, potassium carbonate, and sodiumhydrogencarbonate; and organic bases such as pyridine, triethylamine,ethyldiisopropylamine, and N,N-diethylaniline. Examples of the adjuvantsfor acylation include catalysts such as 4-dimethylaminopyridine andtetrabutylammonium bromide; halogenating agents such as thionylchloride, phosphorus oxychloride, phosphorus trichloride, ethylchloroformate, and 4-nitrobenzenesulfonyl chloride; carbodiimides suchas N,N′-dicyclohexylcarbodiimide and1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide. Any solvent can be usedas long as it does not inhibit the reaction, and examples include esterssuch as ethyl formate, methyl acetate, ethyl acetate, and butyl acetate;halides such as dichloromethane, dichloroethane, and chloroform; etherssuch as tetrahydrofuran, 1,2-dimethoxyethane, and 1,4-dioxane;substituted or unsubstituted benzenes such as benzene, toluene,monochlorobenzene, and 1,2-dichlorobenzene; amides such asN,N-dimethylformamide and N-methylpyrrolidone; alcohols such asmethanol, ethanol, 1-propanol, and 2-propanol; ketones such as acetoneand methyl ethyl ketone; and water. These solvents can be used alone oras a mixture, or as two phase solvents.

<<Preparation Method 2>>

In the compounds represented by the general formula (I) of the presentinvention, the compounds wherein R¹ is a group represented by theformula —O-A wherein A represents hydrogen atom or an acyl group, R² ishydrogen atom, R³ is hydrogen atom, R⁴ is a group represented by thefollowing formula:

wherein R⁵ represents a cyclic group which may be substituted, Zrepresents a single bond or a C₁ to C₄ alkylene group which may besubstituted; or when Z is substituted, said substituent may bind to R⁵to form a ring group, R⁶ represents hydrogen atom or a C₁ to C₆ alkylgroup which may be substituted; or R⁶ may bind to Z or R⁵ to form a ringgroup can be prepared, for example, by a method described in thereaction scheme 2.

5-(Acetyloxy)naphthalene-2-sulfonyl chloride (7) can be prepared, forexample, by the method disclosed in Tetrahedron, volume 48, No. 42, pp.9207-9216(published in 1992) and Japanese Patent Kokoku Sho 60-140240.The amine (2) wherein R⁵, R⁶, and Z have the same meanings as thosedefined in the general formula (I) can be obtained by methods describedin the preparation method 1.

By reacting 5-(acetyloxy)naphthalene-2-sulfonyl chloride (7) with theamine (2) wherein R⁵, R⁶, and Z have the same meanings as those definedin the general formula (I), the compound of the formula (8) wherein R⁵,R⁶, and Z have the same meanings as those defined in the general formula(I) can be obtained. The compound of the formula (8) is encompassedwithin the general formula (I). This reaction is carried out in thepresence or absence of a base and/or a catalyst, with or without asolvent, at a reaction temperature of from −30° C. to a refluxingtemperature of a solvent (at a reaction temperature of from −30° C. to150° C., when the reaction is carried out without a solvent).

Examples of the bases include inorganic bases such as sodium hydroxide,potassium hydroxide, sodium carbonate, potassium carbonate, and sodiumhydrogencarbonate; and organic bases such as pyridine, triethylamine,ethyldiisopropylamine, and N,N-diethylaniline. Examples of the catalystsinclude 4-dimethylaminopyridine and tetrabutylammonium bromide. Anysolvent can be used as long as it does not inhibit the reaction, andexamples include esters such as ethyl formate, methyl acetate, ethylacetate, and butyl acetate; halides such as dichloromethane,dichloroethane, and chloroform; ethers such as tetrahydrofuran,1,2-dimethoxyethane, and 1,4-dioxane; substituted or unsubstitutedbenzenes such as benzene, toluene, monochlorobenzene, and1,2-dichlorobenzene; amides such as N,N-dimethylformamide andN-methylpyrrolidone; alcohols such as methanol, ethanol, 1-propanol, and2-propanol; ketones such as acetone and methyl ethyl ketone; and water.These solvents can be used alone or as a mixture, or as two phasesolvents.

The acetyl group of the resulting compound of the formula (8) whereinR⁵, R⁶, and Z have the same meanings as those defined in the generalformula (I) is then hydrolyzed to prepare the compounds represented bythe formula (9). The compound of the formula (9) is encompassed withinthe general formula (I). This reaction is carried out in the presence ofan acid or a base, with or without a solvent, at a reaction temperatureof from 0° C. to a refluxing temperature of a solvent (at a reactiontemperature of from 0° C. to 150° C., when the reaction is carried outwithout a solvent).

Examples of the acids include mineral acids such as hydrochloric acidand sulfuric acid; organic acids such as formic acid, acetic acid,methanesulfonic acid, and p-toluenesulfonic acid; and Lewis acids suchas alminium chloride and triethyloxonium tetrafluoroborate. Examples ofthe bases include inorganic bases such as sodium hydroxide, potassiumhydroxide, potassium carbonate, and sodium hydrogencarbonate; andorganic bases such as hydrazine. Any solvent can be used as long as itdoes not inhibit the reaction, and examples include ethers such astetrahydrofuran, 1,2-dimethoxyethane, and 1,4-dioxane; alcohols such asmethanol, ethanol, 1-propanol, and 2-propanol; and water. These solventscan be used alone or as a mixture, or as two phase solvents.

The compound of the formula (9) wherein R⁵, R⁶, and Z have the samemeanings as those defined in the general formula (I) is then reactedwith the acylating agent (5) wherein A represents an acyl group, Wrepresents halogen atom; acyloxy group such as acetoxy group, benzoyloxygroup, methanesulfonyl group, and tosyl group; imidoxy group such as(2,5-dioxopyrrolidin-1-yl group; 1-imidazolyl group; and hydroxy group,to prepare the compounds represented by the formula (10), which areencompassed within the general formula (I), wherein A, R⁵, R⁶, and Zhave the same meanings as those defined in the general formula (I). Thisreaction is carried out in the presence or absence of a base and/or anadjuvant for acylation, with or without a solvent, at a reactiontemperature of from −30° C. to a refluxing temperature of a solvent (ata reaction temperature of from −30° C. to 150° C., when the reaction iscarried out without a solvent).

Examples of the bases include inorganic bases such as sodium hydroxide,potassium hydroxide, sodium carbonate, potassium carbonate, and sodiumhydrogencarbonate; and organic bases such as pyridine, triethylamine,ethyldiisopropylamine, and N,N-diethylaniline. Examples of the adjuvantsfor acylation include catalysts such as 4-dimethylaminopyridine andtetrabutylammonium bromide; halogenating agents such as thionylchloride, phosphorus oxychloride, phosphorus trichloride, ethylchloroformate, and 4-nitrobenzenesulfonyl chloride; carbodiimides suchas N,N′-dicyclohexylcarbodiimide and1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide. Any solvent can be usedas long as it does not inhibit the reaction, and examples include esterssuch as ethyl formate, methyl acetate, ethyl acetate, and butyl acetate;halides such as dichloromethane, dichloroethane, and chloroform; etherssuch as tetrahydrofuran, 1,2-dimethoxyethane, and 1,4-dioxane;substituted or unsubstituted benzenes such as benzene, toluene,monochlorobenzene, and 1,2-dichlorobenzene; amides such asN,N-dimethylformamide and N-methylpyrrolidone; alcohols such asmethanol, ethanol, 1-propanol, and 2-propanol; ketones such as acetoneand methyl ethyl ketone; and water. These solvents can be used alone oras a mixture, or as two phase solvents.

<<Preparation Method 3>>

In the compounds represented by the general formula (I) of the presentinvention, the compounds wherein R¹ is a group represented by theformula —NH-A wherein A represents hydrogen atom or an acyl group, R² ishydrogen atom, R³ is hydrogen atom, R⁴ is a group represented by thefollowing formula:

wherein R⁵ represents a cyclic group which may be substituted, Zrepresents a single bond or a C₁ to C₄ alkylene group which may besubstituted; or when Z is substituted, said substituent may bind to R⁵to form a ring group, R⁶ represents hydrogen atom or a C₁ to C₆ alkylgroup which may be substituted; or R⁶ may bind to Z or R⁵ to form a ringgroup can be prepared, for example, by a method described in thereaction scheme 3.

5-(Acetylamino)naphthalene-2-sulfonyl chloride (11) can be prepared, forexample, by the method disclosed in the U.S. Pat. No. 5,378,715. Theamine (2) wherein R⁵, R⁶, and Z have the same meanings as those definedin the general formula (I) can be obtained by methods described in thepreparation method 1.

By reacting 5-(acetylamino)naphthalene-2-sulfonyl chloride (11) with theamine (2) wherein R⁵, R⁶, and Z have the same meanings as those definedin the general formula (I), the compound of the formula (12) wherein R⁵,R⁶, and Z have the same meanings as those defined in the general formula(I) can be obtained. The compound of the formula (12) is encompassedwithin the general formula (I). This reaction is carried out in thepresence or absence of a base and/or a catalyst, with or without asolvent, at a reaction temperature of from −30° C. to a refluxingtemperature of a solvent (at a reaction temperature of from −30° C. to150° C., when the reaction is carried out without a solvent).

Examples of the bases include inorganic bases such as sodium hydroxide,potassium hydroxide, sodium carbonate, potassium carbonate, and sodiumhydrogencarbonate; and organic bases such as pyridine, triethylamine,ethyldiisopropylamine, and N,N-diethylaniline. Examples of the catalystsinclude 4-dimethylaminopyridine and tetrabutylammonium bromide. Anysolvent can be used as long as it does not inhibit the reaction, andexamples include esters such as ethyl formate, methyl acetate, ethylacetate, and butyl acetate; halides such as dichloromethane,dichloroethane, and chloroform; ethers such as tetrahydrofuran,1,2-dimethoxyethane, and 1,4-dioxane; substituted or unsubstitutedbenzenes such as benzene, toluene, monochlorobenzene, and1,2-dichlorobenzene; amides such as N,N-dimethylformamide andN-methylpyrrolidone; alcohols such as methanol, ethanol, 1-propanol, and2-propanol; ketones such as acetone and methyl ethyl ketone; and water.These solvents can be used alone or as a mixture, or as two phasesolvents.

The acetyl group of the resulting compound of the formula (12) whereinR⁵, R⁶, and Z have the same meanings as those defined in the generalformula (I) is then hydrolyzed to prepare the compounds represented bythe formula (13). The compound of the formula (13) is encompassed withinthe general formula (I). This reaction is carried out in the presence ofan acid or a base, with or without a solvent, at a reaction temperatureof from 0° C. to a refluxing temperature of a solvent (at a reactiontemperature of from 0° C. to 150° C., when the reaction is carried outwithout a solvent).

Examples of the acids include mineral acids such as hydrochloric acidand sulfuric acid; and Lewis acids such as triethyloxoniumtetrafluoroborate. Examples of the bases include inorganic bases such assodium hydroxide, potassium hydroxide, and metallic sodium; and organicbases such as hydrazine. Any solvent can be used as long as it does notinhibit the reaction, and examples include ethers such astetrahydrofuran, 1,2-dimethoxyethane, and 1,4-dioxane; alcohols such asmethanol, ethanol, 1-propanol, and 2-propanol; and water. These solventscan be used alone or as a mixture, or as two phase solvents.

The compound of the formula (13) wherein R⁵, R⁶, and Z have the samemeanings as those defined in the general formula (I) is then reactedwith the acylating agent (5) wherein A represents an acyl group, Wrepresents halogen atom; acyloxy group such as acetoxy group, benzoyloxygroup, methanesulfonyl group, and tosyl group; imidoxy group such as(2,5-dioxopyrrolidin-1-yl group; 1-imidazolyl group; and hydroxy group,to prepare the compounds represented by the formula (14), which areencompassed within the general formula (I), wherein A, R⁵, R⁶, and Zhave the same meanings as those defined in the general formula (I). Thisreaction is carried out in the presence or absence of a base and/or anadjuvant for acylation, with or without a solvent, at a reactiontemperature of from −30° C. to a refluxing temperature of a solvent (ata reaction temperature of from −30° C. to 150° C., when the reaction iscarried out without a solvent).

Examples of the bases include inorganic bases such as sodium hydroxide,potassium hydroxide, sodium carbonate, potassium carbonate, and sodiumhydrogencarbonate; and organic bases such as pyridine, triethylamine,ethyldiisopropylamine, and N,N-diethylaniline. Examples of the adjuvantsfor acylation include catalysts such as 4-dimethylaminopyridine andtetrabutylammonium bromide; halogenating agents such as thionylchloride, phosphorus oxychloride, phosphorus trichloride, ethylchloroformate, and 4-nitrobenzenesulfonyl chloride; carbodiimides suchas N,N′-dicyclohexylcarbodiimide and1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide. Any solvent can be usedas long as it does not inhibit the reaction, and examples include esterssuch as ethyl formate, methyl acetate, ethyl acetate, and butyl acetate;halides such as dichloromethane, dichloroethane, and chloroform; etherssuch as tetrahydrofuran, 1,2-dimethoxyethane, and 1,4-dioxane;substituted or unsubstituted benzenes such as benzene, toluene,monochlorobenzene, and 1,2-dichlorobenzene; amides such asN,N-dimethylformamide and N-methylpyrrolidone; alcohols such asmethanol, ethanol, 1-propanol, and 2-propanol; ketones such as acetoneand methyl ethyl ketone; and water. These solvents can be used alone oras a mixture, or as two phase solvents.

<<Preparation Method 4>>

In the compounds represented by the general formula (I) of the presentinvention, the compounds wherein R¹ is hydrogen atom, R² is a grouprepresented by the formula —NH-A wherein A represents hydrogen atom oran acyl group, R³ is a group represented by the following formula:

wherein R⁵ represents a cyclic group which may be substituted, Zrepresents a single bond or a C₁ to C₄ alkylene group which may besubstituted; or when Z is substituted, said substituent may bind to R⁵to form a ring group, R⁶ represents hydrogen atom or a C₁ to C₆ alkylgroup which may be substituted; or R⁶ may bind to Z or R⁵ to form a ringgroup, R⁴ is hydrogen atom can be prepared, for example, by a methoddescribed in the reaction scheme 4.

6-(Acetylamino)naphthalene-1-sulfonyl chloride (15) can be prepared, forexample, by the method disclosed in the U.S. Pat. No. 5,378,715. Theamine (2) wherein R⁵, R⁶, and Z have the same meanings as those definedin the general formula (I) can be obtained by methods described in thepreparation method 1.

By reacting 6-(acetylamino)naphthalene-1-sulfonyl chloride (15) with theamine (2) wherein R⁵, R⁶, and Z have the same meanings as those definedin the general formula (I), the compound of the formula (16) wherein R⁵,R⁶, and Z have the same meanings as those defined in the general formula(I) can be obtained. The compound of the formula (16) is encompassedwithin the general formula (I). This reaction is carried out in thepresence or absence of a base and/or a catalyst, with or without asolvent, at a reaction temperature of from −30° C. to a refluxingtemperature of a solvent (at a reaction temperature of from −30° C. to150° C., when the reaction is carried out without a solvent).

Examples of the bases include inorganic bases such as sodium hydroxide,potassium hydroxide, sodium carbonate, potassium carbonate, and sodiumhydrogencarbonate; and organic bases such as pyridine, triethylamine,ethyldiisopropylamine, and N,N-diethylaniline. Examples of the catalystsinclude 4-dimethylaminopyridine and tetrabutylammonium bromide. Anysolvent can be used as long as it does not inhibit the reaction, andexamples include esters such as ethyl formate, methyl acetate, ethylacetate, and butyl acetate; halides such as dichloromethane,dichloroethane, and chloroform; ethers such as tetrahydrofuran,1,2-dimethoxyethane, and 1,4-dioxane; substituted or unsubstitutedbenzenes such as benzene, toluene, monochlorobenzene, and1,2-dichlorobenzene; amides such as N,N-dimethylformamide andN-methylpyrrolidone; alcohols such as methanol, ethanol, 1-propanol, and2-propanol; ketones such as acetone and methyl ethyl ketone; and water.These solvents can be used alone or as a mixture, or as two phasesolvents.

The acetyl group of the resulting compound of the formula (16) whereinR⁵, R⁶, and Z have the same meanings as those defined in the generalformula (I) is then hydrolyzed to prepare the compounds represented bythe formula (17). The compound of the formula (17) is encompassed withinthe general formula (I). This reaction is carried out in the presence ofan acid or a base, with or without a solvent, at a reaction temperatureof from 0° C. to a refluxing temperature of a solvent (at a reactiontemperature of from 0° C. to 150° C., when the reaction is carried outwithout a solvent).

Examples of the acids include mineral acids such as hydrochloric acidand sulfuric acid; and Lewis acids such as triethyloxoniumtetrafluoroborate. Examples of the bases include inorganic bases such assodium hydroxide, potassium hydroxide, and metallic sodium; and organicbases such as hydrazine. Any solvent can be used as long as it does notinhibit the reaction, and examples include ethers such astetrahydrofuran, 1,2-dimethoxyethane, and 1,4-dioxane; alcohols such asmethanol, ethanol, 1-propanol, and 2-propanol; and water. These solventscan be used alone or as a mixture, or as two phase solvents.

The compound of the formula (17) wherein R⁵, R⁶, and Z have the samemeanings as those defined in the general formula (I) is then reactedwith the acylating agent (5) wherein A represents an acyl group, Wrepresents halogen atom; acyloxy group such as acetoxy group, benzoyloxygroup, methanesulfonyl group, and tosyl group; imidoxy group such as(2,5-dioxopyrrolidin-1-yl group; 1-imidazolyl group; and hydroxy group,to prepare the compounds represented by the formula (18), which areencompassed within the general formula (I), wherein A, R⁵, R⁶, and Zhave the same meanings as those defined in the general formula (I). Thisreaction is carried out in the presence or absence of a base and/or anadjuvant for acylation, with or without a solvent, at a reactiontemperature of from −30° C. to a refluxing temperature of a solvent (ata reaction temperature of from −30° C. to 150° C., when the reaction iscarried out without a solvent).

Examples of the bases include inorganic bases such as sodium hydroxide,potassium hydroxide, sodium carbonate, potassium carbonate, and sodiumhydrogencarbonate; and organic bases such as pyridine, triethylamine,ethyldiisopropylamine, and N,N-diethylaniline. Examples of the adjuvantsfor acylation include catalysts such as 4-dimethylaminopyridine andtetrabutylammonium bromide; halogenating agents such as thionylchloride, phosphorus oxychloride, phosphorus trichloride, ethylchloroformate, and 4-nitrobenzenesulfonyl chloride; carbodiimides suchas N,N′-dicyclohexylcarbodiimide and1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide. Any solvent can be usedas long as it does not inhibit the reaction, and examples include esterssuch as ethyl formate, methyl acetate, ethyl acetate, and butyl acetate;halides such as dichloromethane, dichloroethane, and chloroform; etherssuch as tetrahydrofuran, 1,2-dimethoxyethane, and 1,4-dioxane;substituted or unsubstituted benzenes such as benzene, toluene,monochlorobenzene, and 1,2-dichlorobenzene; amides such asN,N-dimethylformamide and N-methylpyrrolidone; alcohols such asmethanol, ethanol, 1-propanol, and 2-propanol; ketones such as acetoneand methyl ethyl ketone; and water. These solvents can be used alone oras a mixture, or as two phase solvents.

<<Preparation Method 5>>

In the compounds represented by the general formula (I) of the presentinvention, the compounds wherein R¹ is hydrogen atom, R² is a grouprepresented by the formula —NH-A wherein A represents hydrogen atom oran acyl group, R³ is hydrogen atom, R⁴ is a group represented by thefollowing formula:

wherein R⁵ represents a cyclic group which may be substituted, Zrepresents a single bond or a C₁ to C₄ alkylene group which may besubstituted; or when Z is substituted, said substituent may bind to R⁵to form a ring group, R⁶ represents hydrogen atom or a C₁ to C₆ alkylgroup which may be substituted; or R⁶ may bind to Z or R⁵ to form a ringgroup can be prepared, for example, by a method described in thereaction scheme 5.

6-(Acetylamino)naphthalene-2-sulfonyl chloride (19) can be prepared, forexample, by the method disclosed in the U.S. Pat. No. 5,378,715. Theamine (2) wherein R⁵, R⁶, and Z have the same meanings as those definedin the general formula (I) can be obtained by methods described in thepreparation method 1.

By reacting 6-(acetylamino)naphthalene-2-sulfonyl chloride (19) with theamine (2) wherein R⁵, R⁶, and Z have the same meanings as those definedin the general formula (I), the compound of the formula (20) wherein R⁵,R⁶, and Z have the same meanings as those defined in the general formula(I) can be obtained. The compound of the formula (20) is encompassedwithin the general formula (I). This reaction is carried out in thepresence or absence of a base and/or a catalyst, with or without asolvent, at a reaction temperature of from −30° C. to a refluxingtemperature of a solvent (at a reaction temperature of from −30° C. to150° C., when the reaction is carried out without a solvent).

Examples of the bases include inorganic bases such as sodium hydroxide,potassium hydroxide, sodium carbonate, potassium carbonate, and sodiumhydrogencarbonate; and organic bases such as pyridine, triethylamine,ethyldiisopropylamine, and N,N-diethylaniline. Examples of the catalystsinclude 4-dimethylaminopyridine and tetrabutylammonium bromide. Anysolvent can be used as long as it does not inhibit the reaction, andexamples include esters such as ethyl formate, methyl acetate, ethylacetate, and butyl acetate; halides such as dichloromethane,dichloroethane, and chloroform; ethers such as tetrahydrofuran,1,2-dimethoxyethane, and 1,4-dioxane; substituted or unsubstitutedbenzenes such as benzene, toluene, monochlorobenzene, and1,2-dichlorobenzene; amides such as N,N-dimethylformamide andN-methylpyrrolidone; alcohols such as methanol, ethanol, 1-propanol, and2-propanol; ketones such as acetone and methyl ethyl ketone; and water.These solvents can be used alone or as a mixture, or as two phasesolvents.

The acetyl group of the resulting compound of the formula (20) whereinR⁵, R⁶, and Z have the same meanings as those defined in the generalformula (I) is then hydrolyzed to prepare the compounds represented bythe formula (21). The compound of the formula (21) is encompassed withinthe general formula (I). This reaction is carried out in the presence ofan acid or a base, with or without a solvent, at a reaction temperatureof from 0° C. to a refluxing temperature of a solvent (at a reactiontemperature of from 0° C. to 150° C., when the reaction is carried outwithout a solvent).

Examples of the acids include mineral acids such as hydrochloric acidand sulfuric acid; and Lewis acids such as triethyloxoniumtetrafluoroborate. Examples of the bases include inorganic bases such assodium hydroxide, potassium hydroxide, and metallic sodium; and organicbases such as hydrazine. Any solvent can be used as long as it does notinhibit the reaction, and examples include ethers such astetrahydrofuran, 1,2-dimethoxyethane, and 1,4-dioxane; alcohols such asmethanol, ethanol, 1-propanol, and 2-propanol; and water. These solventscan be used alone or as a mixture, or as two phase solvents.

The compound of the formula (21) wherein R⁵, R⁶, and Z have the samemeanings as those defined in the general formula (I) is then reactedwith the acylating agent (5) wherein A represents an acyl group, Wrepresents halogen atom; acyloxy group such as acetoxy group, benzoyloxygroup, methanesulfonyl group, and tosyl group; imidoxy group such as(2,5-dioxopyrrolidin-1-yl group; 1-imidazolyl group; and hydroxy group,to prepare the compounds represented by the formula (22), which areencompassed within the general formula (I), wherein A, R⁵, R⁶, and Zhave the same meanings as those defined in the general formula (I). Thisreaction is carried out in the presence or absence of a base and/or anadjuvant for acylation, with or without a solvent, at a reactiontemperature of from −30° C. to a refluxing temperature of a solvent (ata reaction temperature of from −30° C. to 150° C., when the reaction iscarried out without a solvent).

Examples of the bases include inorganic bases such as sodium hydroxide,potassium hydroxide, sodium carbonate, potassium carbonate, and sodiumhydrogencarbonate; and organic bases such as pyridine, triethylamine,ethyldiisopropylamine, and N,N-diethylaniline. Examples of the adjuvantsfor acylation include catalysts such as 4-dimethylaminopyridine andtetrabutylammonium bromide; halogenating agents such as thionylchloride, phosphorus oxychloride, phosphorus trichloride, ethylchloroformate, and 4-nitrobenzenesulfonyl chloride; carbodiimides suchas N,N′-dicyclohexylcarbodiimide and1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide. Any solvent can be usedas long as it does not inhibit the reaction, and examples include esterssuch as ethyl formate, methyl acetate, ethyl acetate, and butyl acetate;halides such as dichloromethane, dichloroethane, and chloroform; etherssuch as tetrahydrofuran, 1,2-dimethoxyethane, and 1,4-dioxane;substituted or unsubstituted benzenes such as benzene, toluene,monochlorobenzene, and 1,2-dichlorobenzene; amides such asN,N-dimethylformamide and N-methylpyrrolidone; alcohols such asmethanol, ethanol, 1-propanol, and 2-propanol; ketones such as acetoneand methyl ethyl ketone; and water. These solvents can be used alone oras a mixture, or as two phase solvents.

<<Preparation Method 6>>

In the compounds represented by the general formula (I) of the presentinvention, the compounds wherein R¹ is a group represented by theformula —NH-A wherein A represents hydrogen atom or an acyl group, R² ishydrogen atom, R³ is a group represented by the following formula:

wherein R⁵ represents a cyclic group which may be substituted, Zrepresents a single bond or a C₁ to C₄ alkylene group which may besubstituted; or when Z is substituted, said substituent may bind to R⁵to form a ring group, R⁶ represents hydrogen atom or a C₁ to C₆ alkylgroup which may be substituted; or R⁶ may bind to Z or R⁵ to form a ringgroup, R⁴ is hydrogen atom can be prepared, for example, by a methoddescribed in the reaction scheme 6.

5-Nitronaphthalene-1-carboxylic acid (23) can be prepared, for example,by the method disclosed in Tetrahedron, volume 49, No. 17, pp.3655-3663(published in 1993). The amine (2) wherein R⁵, R⁶, and Z havethe same meanings as those defined in the general formula (I) can beobtained by methods described in the preparation method 1.

By reacting 5-nitronaphthalene-1-carboxylic acid (23) with the amine (2)wherein R⁵, R⁶, and Z have the same meanings as those defined in thegeneral formula (I), the compound of the formula (24) wherein R⁵, R⁶,and Z have the same meanings as those defined in the general formula (I)can be obtained. This reaction is carried out in the presence of anadjuvant for acylation and/or a base, with or without a solvent, at areaction temperature of from −30° C. to a refluxing temperature of asolvent (at a reaction temperature of from −30° C. to 150° C., when thereaction is carried out without a solvent).

Examples of the adjuvants for acylation include halogenating agents suchas thionyl chloride, phosphorus oxychloride, phosphorus trichloride,ethyl chloroformate, and 4-nitrobenzenesulfonyl chloride; carbodiimidessuch as N,N′-dicyclohexylcarbodiimide and1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide; andcarbonyldiimidazole. Examples of the bases include organic bases such aspyridine, triethylamine, ethyldiisopropylamine, N,N-diethylaniline, and4-dimethylaminopyridine. Any solvent can be used as long as it does notinhibit the reaction, and examples include esters such as ethyl formate,methyl acetate, ethyl acetate, and butyl acetate; halides such asdichloromethane, dichloroethane, and chloroform; ethers such astetrahydrofuran, 1,2-dimethoxyethane, and 1,4-dioxane; substituted orunsubstituted benzenes such as benzene, toluene, monochlorobenzene, and1,2-dichlorobenzene; amides such as N,N-dimethylformamide andN-methylpyrrolidone; alcohols such as methanol, ethanol, 1-propanol, and2-propanol; ketones such as acetone and methyl ethyl ketone; and water.These solvents can be used alone or as a mixture, or as two phasesolvents.

The nitro group of the resulting compound of the formula (24) whereinR⁵, R⁶, and Z have the same meanings as those defined in the generalformula (I) is then reduced to prepare the compounds represented by theformula (25). The compound of the formula (25) is encompassed within thegeneral formula (I). This reaction is carried out in the presence orabsence of a reducing agent, and an acid or a base, with or without asolvent, at a reaction temperature of from 0° C. to a refluxingtemperature of a solvent (at a reaction temperature of from 0° C. to150° C., when the reaction is carried out without a solvent).

Examples of the reducing agents include noble metals such as palladiumon carbon, palladium black, platinium oxide, and Raney nickel; simplemetals such as sodium, lithium, aluminium, iron, tin, and zinc; andmetal salts such as tin(IV) chloride. Examples of the acids includemineral acids such as hydrochloric acid and sulfuric acid; and organicacids such as formic acid and acetic acid. Examples of the bases includeorganic bases such as triethylamine, pyridine, and quinoline. Anysolvent can be used as long as it does not inhibit the reaction, andexamples include esters such as ethyl formate, methyl acetate, ethylacetate, and butyl acetate; ethers such as tetrahydrofuran,1,2-dimethoxyethane, and 1,4-dioxane; alcohols such as methanol,ethanol, 1-propanol, and 2-propanol; ketones such as acetone and methylethyl ketone; and water. These solvents can be used alone or as amixture, or as two phase solvents.

The compound of the formula (25) wherein R⁵, R⁶, and Z have the samemeanings as those defined in the general formula (I) is then reactedwith the acylating agent (5) wherein A represents an acyl group, Wrepresents halogen atom; acyloxy group such as acetoxy group, benzoyloxygroup, methanesulfonyl group, and tosyl group; imidoxy group such as(2,5-dioxopyrrolidin-1-yl group; 1-imidazolyl group; and hydroxy group,to prepare the compounds represented by the formula (26), which areencompassed within the general formula (I), wherein A, R⁵, R⁶, and Zhave the same meanings as those defined in the general formula (I). Thisreaction is carried out in the presence or absence of a base and/or anadjuvant for acylation, with or without a solvent, at a reactiontemperature of from −30° C. to a refluxing temperature of a solvent (ata reaction temperature of from −30° C. to 150° C., when the reaction iscarried out without a solvent).

Examples of the bases include inorganic bases such as sodium hydroxide,potassium hydroxide, sodium carbonate, potassium carbonate, and sodiumhydrogencarbonate; and organic bases such as pyridine, triethylamine,ethyldiisopropylamine, and N,N-diethylaniline. Examples of the adjuvantsfor acylation include catalysts such as 4-dimethylaminopyridine andtetrabutylammonium bromide; halogenating agents such as thionylchloride, phosphorus oxychloride, phosphorus trichloride, ethylchloroformate, and 4-nitrobenzenesulfonyl chloride; carbodiimides suchas N,N′-dicyclohexylcarbodiimide and1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide. Any solvent can be usedas long as it does not inhibit the reaction, and examples include esterssuch as ethyl formate, methyl acetate, ethyl acetate, and butyl acetate;halides such as dichloromethane, dichloroethane, and chloroform; etherssuch as tetrahydrofuran, 1,2-dimethoxyethane, and 1,4-dioxane;substituted or unsubstituted benzenes such as benzene, toluene,monochlorobenzene, and 1,2-dichlorobenzene; amides such asN,N-dimethylformamide and N-methylpyrrolidone; alcohols such asmethanol, ethanol, 1-propanol, and 2-propanol; ketones such as acetoneand methyl ethyl ketone; and water. These solvents can be used alone oras a mixture, or as two phase solvents.

Examples of preparation methods of the salts of the compoundsrepresented by the general formula (I) include a direct preparation ofsalts by a hydrolysis of the compounds of the aforementioned formulas(3), (8), (12), (16), or (20), or a reduction of the compounds of theaforementioned formula (24); and a preparation wherein the free form ofthe compounds represented by the general formula (I) is first preparedby the above hydrolysis or reduction, and then the free form isconverted to salts. These methods are easily understood by those skilledin the art.

In the examples of the specification, methods for preparation of typicalcompounds falling within the general formula (I) are explained indetail. Accordingly, those skilled in the art can prepare any compoundencompassed within the general formula (I) by referring to the generalexplanations of the aforementioned preparation methods and specificexplanations of the preparation methods of the examples, and by choosingappropriate starting materials, reagents, and reaction conditions and byadding appropriate modification and alteration to these methods, ifnecessary.

Medicaments of the present invention can be used to enhance the effectof cancer therapy based on the mode of action of DNA injury, includingcancer chemotherapies by using anticancer agents and radiation therapiesof cancer that induce DNA injury. Typical examples of anticancer agentsthat induces DNA injury include bleomycin, adriamycin, cisplatin,cyclophosphamide, and mitomycinC. Besides these derivatives, any ofanticancer agents involving the mode of action of DNA injury can betargets of the medicaments of the present invention. The medicaments ofthe present invention may be used where either of a cancer chemotherapyusing anticancer agents or a radiation therapy of cancer that induce DNAinjury is solely carried out, or in a cancer therapy where a combinationof these therapies is carried out.

As the active ingredient of the medicament of the present invention, ahydrate or a solvate of the compounds represented by the aforementionedgeneral formulas (I) or pharmacologically acceptable salts thereof maybe used. Furthermore, when the compound contains one or more asymmetriccarbon atoms, any of a pure form of optically active compound or anymixture of optically active compounds, or a racemate may be used. As theactive ingredient of the medicament of the present invention, one ormore kinds of substances selected from the group consisting of theaforementioned compound and a pharmacologically acceptable salt thereof,and a hydrate thereof and a solvate thereof may be used.

As the medicament of the present invention, the aforementionedsubstance, per se, may be administered. Preferably, the medicament maybe administered as a pharmaceutical composition for oral or parenteraladministration that may be prepared by methods well known to thoseskilled in the art. Examples of pharmaceutical compositions suitable fororal administration include tablets, capsules, powders, subtilizedgranules, granules, solution, and syrup, and examples of pharmaceuticalcompositions suitable for parenteral administration include injections,suppositories, inhalants, instillations, nasal drops, ointments,percutaneous absorbents, transmucosal absorptions, cream, and plaster.

The aforementioned pharmaceutical compositions can be prepared by addingpharmacologically and pharmaceutically acceptable additives. Examples ofpharmacologically and pharmaceutically acceptable additives includeexcipients, disintegrators or disintegration aids, binders, lubricants,coating agents, colorants, diluents, base materials, dissolving aids ordissolution adjuvants, isotonizing agents, pH modifiers, stabilizers,propellants, and adhesives. One or more kinds of anticancer agents basedon the mode of action of DNA injury may be added to the aforementionedpharmaceutical compositions.

A dose of the medicament of the present invention is not particularlylimited. The dose may be selected appropriately depending on a kind ofthe active ingredient and a kind of a cancer therapy. Further, the dosemay be appropriately increased or decreased depending on various factorsthat should be generally considered such as the weight and age of apatient, a kind and symptom of a disorder, and an administration route.Generally, for an oral administration, the medicament may be used in arange of 0.01 to 1,000 mg for an adult per day.

EXAMPLES

The present invention will be explained more specifically with referenceto the following examples. However the scope of the present invention isnot limited to the following examples.

Example 1 Preparation ofN-benzyl-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide(Compound No. 1-1) (1) Preparation of5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonyl chloride

This compound was prepared by the preparation method disclosed in theU.S. Pat. No. 5,378,715.

¹H-NMR(CDCl₃): δ 2.46(3H, s), 7.33-7.35(3H, m), 7.59(1H, dd, J=8.4, 7.8Hz), 7.70(1H, dd, J=8.4, 7.8 Hz), 7.79(2H, d, J=8.4 Hz), 8.38(1H, dd,J=7.8, 1.2 Hz), 8.40(1H, dd, J=8.4, 0.9 Hz), 8.70(1H, d, J=8.7 Hz).

(2) Preparation ofN-benzyl-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide

Triethylamine (0.17 ml, 1.2 mmol) was added to benzylamine (117.9 mg,1.1 mmol) dissolved in tetrahydrofuran (5 ml). After the solution wascooled in the ice bath,5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonyl chloride (396.9mg, 1.2 mmol) was added, and the mixture was stirred at room temparaturefor 1 hour. The reaction mixture was poured into diluted hydrochloricacid and extracted with ethyl acetate. After the organic layer waswashed with saturated brine, dried over anhydrous sodium sulfate, theresidue obtained by evaporation of the solvent under reduced pressurewas purified by column chromatography on silica gel (eluent; n-hexane :ethyl acetate=2:1) and crystallized (ethyl acetate/hexane) to give thetitle compound as a white crystal (398.8 mg, 85.3%).

¹H-NMR(DMSO-d₆): δ 2.41(3H, s), 4.04(2H, d, J=6.0 Hz), 7.06-7.14(5H, m),7.35(1H, d, J=7.5 Hz), 7.47(2H, d, J=8.4 Hz), 7.61(1H, dd, J=8.4, 7.2Hz), 7.69(1H, dd, J=8.4, 8.1 Hz), 7.85(2H, d, J=8.4 Hz), 8.10(1H, d,J=8.7 Hz), 8.13(1H, d, J=7.5 Hz), 8.61(1H, d, J=8.7 Hz), 8.64(1H, t,J=6.0 Hz).

Example 2 to Example 27

The following compounds were prepared in the same manner as the methodof Example 1(2).

Example 2 (Compound 1-2); Yield: 89.0%

(DMSO-d₆): δ 2.41(3H, s), 4.07(2H, d, J=5.7 Hz), 6.74(2H, t, J=7.8 Hz),7.10-7.20(1H, m), 7.31(1H, dd, J=7.8, 0.9 Hz), 7.48(2H, d, J=8.4 Hz),7.59(1H, dd, J=8.4, 7.2 Hz), 7.64(1H, dd, J=8.7, 7.8 Hz), 7.84(2H, d,J=8.4 Hz), 8.08(1H, ddd, J=8.7, 7.5, 1.2 Hz), 8.53(1H, d, J=9.0 Hz),8.66(1H, t, J=5.7 Hz).

Example 3 (Compound 1-3); Yield: 86.9%

(DMSO-d₆): δ 2.41(3H, s), 4.11(2H, d, J=5.7 Hz), 7.18(1H, dd, J=8.4, 2.1Hz), 7.27(1H, d, J=8.7 Hz), 7.34-7.37(2H, m), 7.47(2H, d, J=8.4 Hz),7.59(1H, dd, J=8.4, 7.5 Hz), 7.69(1H, dd, J=8.4, 8.1 Hz), 7.84(2H, d,J=8.4 Hz), 8.08(1H, d, J=3.0 Hz), 8.11(1H, s), 8.58(1H, d, J=8.1 Hz),8.73(1H, t, J=5.7 Hz).

Example 4 (Compound 1-4); Yield: 98.5

(DMSO-d₆): δ 2.42(3H, s), 4.03(2H, d, J=7.2 Hz), 7.28(1H, d, J=7.5 Hz),7.33(1H, dd, J=8.7, 7.5 Hz), 7.46-7.49(3H, m), 7.57(1H, dd, J=8.4, 7.5Hz), 7.68(1H, dd, J=8.7, 7.5 Hz), 7.85(2H, d, J=8.4 Hz), 7.89-7.91(2H,m), 8.05(1H, d, J=8.7 Hz), 8.12(1H, dd, J=7.2, 1.2 Hz), 8.56(1H, d,J=8.7 Hz), 8.86(1H, t, J=6.3 Hz).

Example 5 (Compound 1-5); Yield: 90.9%

(DMSO-d₆): δ 2.42(3H, s), 4.19(2H, d, J=6.3 Hz), 7.32(1H, dd, J=7.8, 0.9Hz), 7.37(2H, d, J=9.0 Hz), 7.48(2H, dd, J=8.7, 0.9 Hz), 7.62(1H, dd,J=8.4, 7.2 Hz), 7.70(1H, dd, J=8.4, 7.8 Hz), 7.85(2H, d, J=8.1 Hz),7.99(2H, d, J=8.7 Hz), 8.10(1H, dt, J=8.7, 0.9 Hz), 8.14(1H, dd, J=7.5,1.2 Hz), 8.58(1H, d, J=8.7 Hz), 8.85(1H, t, J=6.3 Hz).

Example 6 (Compound 1-6); Yield: 83.3%

(DMSO-d₆): δ 2.03(3H, s), 2.41(3H, s), 4.00(2H, d, J=5.7 Hz),6.94-7.00(2H, m), 7.06(2H, t, J=6.3 Hz), 7.37(1H, d, J=7.2 Hz), 7.47(2H,d, J=8.4 Hz), 7.61(1H, dd, J=8.7, 7.2 Hz), 7.69(1H, dd, J=8.7, 7.8 Hz),7.85(2H, d, J=8.1 Hz), 8.10(1H, d, J=8.7 Hz), 8.12(1H, dd, J=6.3, 1.2Hz), 8.46(1H, t, J=6.0 Hz), 8.64(1H, d, J=8.4 Hz).

Example 7 (Compound 1-7); Yield: 77.3%

(DMSO-d₆): δ 1.19(9H, s), 2.40(3H, s), 3.98(2H, d, J=6.0 Hz), 6.97(2H,d, J=8.5 Hz), 7.12(2H, d, J=8.4 Hz), 7.34(1H, d, J=7.8 Hz), 7.46(2H, d,J=8.1 Hz), 7.59(1H, dd, J=8.4, 7.5 Hz), 7.68(1H, dd, J=8.7, 7.8 Hz),7.84(2H, d, J=8.7 Hz), 8.08(1H, d, J=7.8 Hz), 8.11(1H, d, J=7.2 Hz),8.57(1H, t, J=6.0 Hz), 8.60(1H, d, J=8.7 Hz).

Example 8 (Compound 1-8); Yield: 86.1%

(CDCl₃): δ 2.44(3H, s), 4.28(2H, d, J=6.6 Hz), 5.00(1H, t, J=6.6 Hz),7.29-7.34(6H, m), 7.48(1H, dd, J=8.4, 7.5 Hz), 7.50-7.53(1H, m),7.55(1H, dd, J=9.0, 7.5 Hz), 7.76(2H, d, J=8.4 Hz), 8.19(1H, dt, J=8.7,1.2 Hz), 8.25(1H, dd, J=7.5, 1.2 Hz), 8.51(1H, dt, J=9.0, 0.9 Hz).

Example 9 (Compound 1-9); Yield: 93.3%

(DMSO-d₆): δ 2.41(3H, s), 4.14(2H, d, J=6.0 Hz), 7.30(2H, d, J=8.4 Hz),7.34(1H, dd, J=7.5, 0.6 Hz), 7.47(4H, d, J=8.7 Hz), 7.60(1H, dd, J=8.7,7.5 Hz), 7.70(1H, dd, J=8.7, 7.5 Hz), 7.84(2H, d, J=8.1 Hz), 8.09(1H, d,J=8.4 Hz), 8.12(1H, dd, J=7.5, 1.2 Hz d, J=8.7 Hz), 8.77(1H, t, J=6.3Hz).

Example 10 (Compound 1-10); Yield: 36.9

(CDCl₃): δ 2.47(3H, s), 3.97(2H, d, J=5.7 Hz), 5.03(1H, t, J=6.0 Hz),5.49(2H, s), 6.24(1H, d, J=2.4 Hz), 6.34(1H, dd, J=8.1, 2.1 Hz),6.54(1H, d, J=7.8 Hz), 7.24(1H, dd, J=7.2, 1.2 Hz), 7.37(2H, dd, 8.7,0.9 Hz), 7.49-7.54(2H, m), 7.884(2H, dt, J=8.4, 1.8 Hz), 8.22-8.26(2H,m), 8.52(1H, d, J=8.7 Hz).

Example 11 (Compound 1-11); Yield: 88.1%

(CDCl₃): δ 2.44(3H, s), 3.35(3H, s), 4.12(2H, d, J=6.9 Hz), 5.45(1H, t,J=6.6 Hz), 6.33(1H, d, J=8.1 Hz), 6.59(1H, td, J=7.5, 0.9 Hz), 6.79(1H,dd, J=7.5, 1.8 Hz), 6.97(1H, td, J=7.8, 1.8 Hz), 7.28-7.35(4H, m),7.51(1H, t, J=8.4 Hz), 7.77(2H, d, J=8.1 Hz), 8.02(1H, dd, J=8.4, 0.9Hz), 8.06(1H, dd, J=7.5, 1.2 Hz), 8.45(1H, d, J=9.0 Hz).

Example 12 (Compound 1-12); Yield: 86.6%

(DMSO-d₆): δ 2.41(3H, s), 3.53(3H, s), 4.02(2H, d, J=6.3 Hz),6.60-6.67(3H, m), 7.02(1H, t, J=8.1 Hz), 7.34(1H, dd, J=7.8, 1.2 Hz),7.47(2H, d, J=8.4 Hz), 7.60(1H, dd, J=8.7, 7.5 Hz), 7.69(1H, dd, J=8.7,8.1 Hz), 7.85(2H, d, J=8.4 Hz), 8.09(1H, d, J=8.4 Hz), 8.12(1H, dd,J=7.2, 0.9 Hz), 8.61(1H, d, J=8.7 Hz), 8.64(1H, t, J=6.0 Hz).

Example 13 (Compound 1-13); Yield: 89.7%

(DMSO-d₆): δ 2.41(3H, s), 3.52(3H, s), 3.73(3H, s), 4.03(2H, d, J=6.0Hz), 6.71(1H, dd, J=6.9, 2.1 Hz), 6.79-6.86(2H, m), 7.35(1H, d, J=8.1Hz), 7.47(2H, d, J=8.1 Hz), 7.63(1H, dd, J=8.4, 7.5 Hz), 7.69(1H, dd,J=8.4, 8.1 Hz), 7.85(2H, d, J=8.4 Hz), 8.11(1H, d, J=8.4 Hz), 8.15(1H,d, J=7.2 Hz), 8.48(1H, t, J=6.0 Hz), 8.63(1H, d, J=8.7 Hz).

Example 14 (Compound 1-14); Yield: 94.2%

(CDCl₃): δ 2.44(3H, s), 3.60(6H, s), 4.04(2H, d, J=6.3 Hz), 4.93(1H, t,J=5.4 Hz), 6.14(2H, d, J=2.1 Hz), 6.24(1H, t, J=2.1 Hz), 7.29-7.33(3H,m), 7.48(1H, dd, J=8.4, 7.5 Hz), 7.56(1H, t, J=8.4 Hz), 7.78(2H, d,J=8.7 Hz), 8.19(1H, d, J=8.7 Hz), 8.26(1H, d, J=7.5 Hz), 8.57(1H, d,J=8.7 Hz).

Example 15 (Compound 1-15); Yield: 94.4%

(DMSO-d₆): δ 2.41(3H, s), 3.94(2H, d, J=6.3 Hz), 5.89(2H, s), 6.50(1H,dd, J=8.1, 1.5 Hz), 6.57(1H, d, J=1.2 Hz), 6.62(1H, d, J=8.1 Hz),7.33(1H, dd, J=7.8, 0.9 Hz), 7.47(2H, d, J=7.8 Hz), 7.61(1H, dd, J=8.7,7.2 Hz), 7.68(1H, dd, J=8.7, 7.8 Hz), 7.84(2H, d, J=8.4 Hz), 8.09(1H, d,J=8.7 Hz), 8.11(1H, dd, J=7.5, 1.2 Hz), 8.55(1H, t, J=6.3 Hz), 8.58(1H,d, J=9.0 Hz).

Example 16 (Compound 1-16); Yield: 85.4%

(DMSO-d₆): δ 2.41(3H, s), 3.84(2H, d, J=6.0 Hz), 5.02(2H, s), 6.23(1H,d, J=7.8 Hz), 6.37(1H, d, J=7.5 Hz), 6.42(1H, s), 6.81(1H, t, J=7.8 Hz),7.35(1H, d, J=7.8 Hz), 7.47(2H, d, J=8.4 Hz), 7.64(1H, t, J=7.5 Hz),7.69(1H, t, J=7.8 Hz), 7.85(2H, d, J=8.4 Hz), 8.11-8.15(2H, m), 8.50(1H,t, J=6.0 Hz), 8.63(1H, d, J=8.7 Hz).

Example 17 (Compound 1-17); Yield: 88.3%

(DMSO-d₆): δ 2.40(3H, s), 2.80(6H, s), 3.89(2H, d, J=6.0 Hz), 6.47(2H,d, J=8.7 Hz), 6.86(2H, d, J=8.7 Hz), 7.34(1H, dd, J=7.8, 0.9 Hz),7.46(2H, d, J=8.1 Hz), 7.61(1H, dd, J=8.7, 7.2 Hz), 7.68(1H, dd, J=8.7,7.5 Hz), 7.84(2H, d, J=8.4 Hz), 8.08-8.14(2H, m), 8.42(1H, t, J=6.0 Hz),8.60(1H, d, J=8.7 Hz).

Example 18 (Compound 1-18); Yield: 86.9%

(DMSO-d₆): δ 2.41(3H, s), 3.14(3H, s), 4.16(2H, d, J=6.3 Hz), 7.35(1H,d, J=7.2 Hz), 7.37(2H, d, J=8.1 Hz), 7.48(2H, d, J=8.4 Hz), 7.62(1H, dd,J=8.7, 7.5 Hz), 7.70(2H, d, J=8.1 Hz), 7.76(1H, t, J=4.8 Hz), 7.85(2H,d, J=8.4 Hz), 8.11-8.14(2H, m), 8.60(1H, d, J=8.7 Hz), 8.81(1H, t, J=6.3Hz).

Example 19 (Compound 1-19); Yield: 87.1%

(DMSO-d₆): δ 2.40(3H, s), 4.47(2H, d, J=5.7 Hz), 7.28-7.34(4H, m),7.42(1H, d J=7.5 Hz), 7.47(2H, d, J=8.1 Hz), 7.58(1H, dd, J=8.4, 7.2Hz), 7.64(1H, dd, J=8.7, 7.8 Hz), 7.76(1H, dd, J=7.5, 1.8 Hz),7.83-7.89(4H, m), 8.08(1H, d, J=8.4 Hz), 8.13(1H, dd, J=7.2, 0.9 Hz),8.62(1H, d, J=8.7 Hz), 8.65(1H, t, J=5.4 Hz).

Example 20 (Compound 1-20); Yield: 87.9%

(DMSO-d₆): δ 1.82(3H, s), 2.42(3H, s), 4.01(2H, d, J=6.0 Hz), 5.65(1H,dd, J=3.0, 1.2 Hz), 5.79(1H, d, J=3.0 Hz), 7.33(1H, dd, J=7.5, 0.9 Hz),7.48(2H, d, J=8.7 Hz), 7.61(1H, dd, J=8.7, 7.8 Hz), 7.67(1H, dd, J=8.7,7.8 Hz), 7.86(2H, d, J=8.7 Hz), 8.09(1H, t, J=7.8 Hz), 8.10(1H, t, J=7.8Hz), 8.55-8.61(2H, m).

Example 21 (Compound 1-21); Yield: 91.9%

(DMSO-d₆): δ 2.41(3H, s), 4.14(2H, d, J=6.3 Hz), 7.08-7.16(2H, m),7.35(1H, d, J=7.2 Hz), 7.48(2H, d, J=8.1 Hz), 7.50-7.55(1H, m), 7.59(1H,dd, J=8.7, 7.5 Hz), 7.70(1H, t, J=8.1 Hz), 7.85(2H, d, J=8.7 Hz),8.09(1H, d, J=8.4 Hz), 8.12(1H, dd, J=7.5, 1.2 Hz), 8.23-8.26(1H, m),8.62(1H, d, J=8.7 Hz), 8.76(1H, t, J=6.3 Hz).

Example 22 (Compound 1-22); Yield: 93.7%

(DMSO-d₆): δ 2.41(3H, s), 4.22(2H, d, J=5.7 Hz), 7.12(1H, d, J=2.7 Hz),7.14(1H, d, J=3.0 Hz), 7.34(1H, d, J=7.2 Hz), 7.42(1H, d, J=3.6 Hz),7.44(1H, d, J=3.6 Hz), 7.47(2H, d, J=8.4 Hz), 7.62(1H, dd, J=8.7, 7.5Hz), 7.70(1H, dd, J=8.7, 7.8 Hz), 7.84(2H, d, J=8.7 Hz), 8.10(1H, d,J=8.7 Hz), 8.19(1H, dd, J=7.2, 0.9 Hz), 8.64(1H, d, J=8.7 Hz), 8.83(1H,t, J=5.7 Hz).

Example 23 (Compound 1-23); Yield: 88.7%

(DMSO-d₆): δ 0.61-0.72(2H, m), 0.95-1.04(3H, m), 1.19(1H, bs),1.49-1.52(5H, m), 2.40(3H, s), 2.61(2H, t, J=6.3 Hz), 7.46(1H, d, J=7.8Hz), 7.46(2H, d, J=8.4 Hz), 7.66(1H, t, J=7.8 Hz), 7.70(1H, dd, J=8.7,7.8 Hz), 7.84(2H, d, J=8.4 Hz), 8.04(1H, t, J=6.0 Hz), 8.14(2H, d, J=7.8Hz), 8.62(1H, d, J=9.0 Hz).

Example 24 (Compound 1-24); Yield: 87.8%

(CDCl₃): δ 2.42(3H, s), 6.67(1H, s), 6.88-6.91(2H, m), 7.07-7.19(2H, m),7.25-7.27(3H, m), 7.33-7.38(2H, m), 7.57(1H, dd, J=8.7, 7.8 Hz),7.72(2H, d, J=8.4 Hz), 8.12(1H, dt, J=7.8, 0.9 Hz), 8.16(1H, dd, J=7.5,1.2 Hz), 8.58(1H, d, J=8.7 Hz).

Example 25 (Compound 1-25); Yield: 98.3%

(DMSO-d₆): δ 2.36(3H, s), 2.57(2H, t, J=7.2 Hz), 3.00-3.06(2H, m),7.00(2H, dd, J=8.1, 2.1 Hz), 7.10-7.18(3H, m), 7.37(2H, d, J=7.5 Hz),7.43(2H, d, J=8.7 Hz), 7.63(1H, dd, J=8.4, 7.2 Hz), 7.68(1H, t, J=8.4Hz), 7.83(2H, d, J=8.4 Hz), 8.12(1H, d, J=8.7 Hz), 8.13(1H, J=7.5 Hz),8.18(1H, t, J=6.0 Hz), 8.57(1H, d, J=8.7 Hz).

Example 26 (Compound 1-26); Yield: 81.5%

(DMSO-d₆): δ 1.15(3H, d, J=6.9 Hz), 2.40(3H, s), 4.26-4.36(1H, m),6.90-6.97(5H, m), 7.34(1H, d, J=7.2 Hz), 7.45(2H, d, J=8.4 Hz), 7.48(1H,dd, J=8.7, 7.5 Hz), 7.67(1H, t, J=8.1 Hz), 7.82(2H, d, J=8.1 Hz),7.99(1H, d, J=8.7 Hz), 8.01(1H, d, J=7.5 Hz), 8.58(1H, d, J=3.0 Hz),8.60(1H, d, J=2.7 Hz).

Example 27 (Compound 1-27); Yield: 53.6%

(CDCl₃): δ 2.43(3H, s), 2.70(3H, s), 4.33(2H, s), 7.19-7.22(2H, m),7.27-7.34(6H, m), 7.52(1H, dd, J=8.7, 7.8 Hz), 7.57(1H, dd, J=8.7, 7.8Hz), 7.78(2H, d, J=8.4 Hz), 8.21-8.25(2H, m), 8.72(1H, d, J=8.4 Hz).

Example 28 Preparation of N-benzyl-5-hydroxynaphthalene-1-sulfonamide(Compound No. 2-1)

Methanol (5 ml) and 5N aqueous sodium hydroxide (0.65 ml) were added to5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide (Compound No.1-1; 298.8 mg, 0.64 mmol), and the mixture was stirred at 65° C. for 1hour. After cooling to room temperature, the reaction mixture was pouredinto diluted hydrochloric acid and extracted with ethyl acetate. Afterthe organic layer was washed with saturated brine, dried over anhydroussodium sulfate, the residue obtained by evaporation of the solvent underreduced pressure was purified by column chromatography on silica gel(eluent; n-hexane : ethyl acetate=3:2→1:1) to give the title compound asa light brown white crystal (152.8 mg, 76.2%).

¹H-NMR(DMSO-d₆): δ 4.00(2H, d, J=6.0 Hz), 7.00(1H, d, J=7.5 Hz),7.14-7.22(5H, m), 7.49(1H, dd, J=8.7, 7.5 Hz), 7.52(1H, dd, J=8.1, 7.5Hz), 8.08-8.11(2H, m), 8.42(1H, d, J=8.1 Hz), 8.43(1H, t, J=6.0 Hz),10.49(1H, s).

Example 29 to Example 53

The following compounds were prepared in the same manner as the methodof Example 28. The compounds prepared in Example 2 to Example 9, andExample 11 to Example 27 were used as the law materials.

Example 29 (Compound 2-2); Yield: 76.2%

(DMSO-d₆): δ 4.05(2H, d, J=6.0 Hz), 6.83(2H, t, J=7.8 Hz), 6.97(1H, d,J=7.8 Hz), 7.16-7.27(1H, m), 7.43(1H, t, J=8.7 Hz), 7.49(1H, dd, J=8.1,7.5 Hz), 8.01(1H, d, J=9.0 Hz), 8.06(1H, dd, J=7.2, 1.2 Hz), 8.38(1H, d,J=8.1 Hz), 8.41(1H, t, J=5.7 Hz), 10.43(1H, s).

Example 30 (Compound 2-3); Yield: 76.1%

(DMSO-d₆): δ 4.08(2H, d, J=6.0 Hz), 7.00(1H, d, J=7.8 Hz), 7.21(1H, dd,J=8.4, 2.4 Hz), 7.33(1H, d, J=8.7 Hz), 7.41(1H, d, J=1.8 Hz),7.45-7.53(2H, m), 8.04(1H, d, J=8.1 Hz), 8.07(1H, dd, J=7.2, 1.2 Hz),8.40(1H, d, J=8.4 Hz), 8.53(1H, t, J=6.0 Hz), 10.49(1H, s).

Example 31 (Compound 2-4); Yield: 69.4%

(DMSO-d₆): δ 4.17(2H, d, J=6.3 Hz), 6.95(1H, d, J=7.2 Hz), 7.37(1H, t,J=7.8 Hz), 7.43-7.52(3H, m), 7.89-7.94(2H, m), 8.02(1H, d, J=8.7 Hz),8.06(1H, dd, J=7.5, 1.2 Hz), 8.34(1H, d, J=8.7 Hz), 8.63(1H, t, J=6.3Hz), 10.45(1H, s).

Example 32 (Compound 2-5); Yield: 48.5%

(DMSO-d₆): δ 4.15(2H, d, J=6.3 Hz), 6.99(1H, d, J=7.2 Hz), 7.39(2H, d,J=8.7 Hz), 7.46-7.52(2H, m), 7.99(2H, d, J=8.7 Hz), 8.04(1H, d, J=9.0Hz), 8.07(1H, dd, H=7.2, 1.2 Hz), 8.38(1H, d, J=8.7 Hz), 8.63(1H, t,J=6.3 Hz), 10.61(1H, s).

Example 33 (Compound 2-6); Yield: 73.6%

(DMSO-d₆): δ 2.09(3H, s), 3.97(2H, d, J=6.0 Hz), 6.99-7.12(4H, m),7.15(1H, d, J=7.2 Hz), 7.48(1H, dd, J=8.4, 7.8 Hz), 7.52(1H, dd, J=8.7,7.5 Hz), 8.09(1H, dd, J=7.2, 1.2 Hz), 8.11(1H, d, J=8.1 Hz), 8.52(1H, t,J=6.0 Hz), 8.42(1H, dt, J=8.4, 1.2 Hz), 10.48(1H, s).

Example 34 (Compound 2-7); Yield: 62.8%

(DMSO-d₆): δ 1.20(9H, s), 3.95(2H, d, J=6.0 Hz), 6.99(1H, dd, J=7.8, 0.6Hz), 7.03(2H, d, J=8.7 Hz), 7.15(2H, d, J=8.4 Hz), 7.44-7.52(2H, m),8.05-8.08(2H, m), 8.35(1H, t, J=6.0 Hz), 8.39(1H, dd, J=8.4, 1.2 Hz),10.46(1H, s).

Example 35 (Compound 2-8); Yield: 40.7%

(DMSO-d₆): δ 4.19(2H, d, J=5.7 Hz), 7.01(1H, d, J=7.8 Hz), 7.38(1H, t,J=7.8 Hz), 7.45-7.61(4H, m), 8.05-8.11(2H, m), 8.41(1H, d, J=8.4 Hz),8.61(1H, t, J=6.0 Hz), 10.50(1H, s).

Example 36 (Compound 2-9); Yield: 79.6%

(DMSO-d₆): δ 4.10(2H, d, J=6.3 Hz), 7.00(1H, d, J=6.9 Hz), 7.36(2H, d,J=7.8 Hz), 7.46-7.52(4H, m), 8.05(1H, d, J=8.7 Hz), 8.07(1H, dd, J=7.5,1.2 Hz), 8.40(1H, d, J=8.1 Hz), 8.55(1H, t, J=6.3 Hz), 10.60(1H, s).

Example 37 (Compound 2-11); Yield: 72.2%

(DMSO-d₆): δ 3.64(3H, s), 3.98(2H, d, J=6.3 Hz), 6.73-6.79(2H, m),6.99(1H, d, J=7.2 Hz), 7.10-7.19(2H, m), 7.48(1H, t, J=8.7 Hz), 7.50(1H,t, J=7.8 Hz), 8.06(1H, dd, J=7.5, 1.2 Hz), 8.09(1H, d, J=8.7 Hz),8.17(1H, t, J=6.3 Hz), 8.40(1H, d, J=8.4 Hz), 10.46(1H, s).

Example 38 (Compound 2-12); Yield: 74.9%

(DMSO-d₆): δ 3.54(3H, s), 4.00(2H, d, J=6.3 Hz), 6.64-6.73(3H, m),7.00(1H, d, J=7.8 Hz), 7.08(1H, t, J=7.8 Hz), 7.46-7.53(2H, m), 8.08(1H,dd, J=7.2, 1.5 Hz), d, J=8.4 Hz), 8.41(1H, d, J=7.2 Hz), 8.42(1H, t,J=5.7 Hz), 10.47(1H, s).

Example 39 (Compound 2-13); Yield: 63.1%

(DMSO-d₆): δ 3.56(3H, s), 3.74(3H, s), 4.00(2H, d, J=6.0 Hz), 6.81(1H,dd, J=6.0, 3.3 Hz), 6.86-6.90(2H, m), 7.00(1H, dd, J=7.5, 0.3 Hz),7.48(1H, dd, J=8.7, 7.5 Hz), 7.53(1H, dd, J=8.4, 7.5 Hz), 8.08-8.11(2H,m), 8.27(1H, t, J=6.0 Hz), 8.42(1H, d, J=8.4 Hz), 10.49(1H, s).

Example 40 (Compound 2-14); Yield: 60.8%

(DMSO-d₆): δ 3.52(6H, s), 3.98(2H, d, J=6.3 Hz), 6.21-6.24(3H, m),7.00(1H, d, J=7.8 Hz), 7.48(1H, t, J=8.7, 4.5 Hz), 7.51(1H, dd, J=7.5,3.9 Hz), 8.08(1H, dd, J=5.7, 1.2 Hz), 8.10(1H, d, J=5, 7 Hz), 8.40(1H,d, J=7.2 Hz), 8.42(1H, t, J=6.0 Hz), 10.48(1H, s).

Example 41 (Compound 2-15); Yield: 70.3%

(DMSO-d₆): δ 3.91(2H, d, J=6.3 Hz), 5.90(2H, s), 6.57(1H, dd, J=7.8, 1.8Hz), 6.61(1H, d, J=1.8 Hz), 6.67(1H, d, J=8.1 Hz), 6.99(1H, d, J=7.2Hz), 7.48(1H, dd, J=9.0, 7.5 Hz), 7.50(1H, dd, J=8.7, 7.5 Hz),8.04-8.07(2H, m), 8.34(1H, t, J=6.3 Hz), 8.40(1H, d, J=8.4 Hz),10.46(1H, s).

Example 42 (Compound 2-16); Yield: 79.5%

(DMSO-d₆): δ 3.82(2H, d, J=6.3 Hz), 5.04(2H, s), 6.31(1H, d, J=7.2 Hz),6.40(1H, dd, J=8.1, 1.5 Hz), 6.47(1H, d, J=1.5 Hz), 6.86(1H, t, J=7.8Hz), 7.00(1H, d, J=7.2 Hz), 7.48(1H, dd, J=8.4, 7.2 Hz), 7.54(1H, dd,J=8.4, 7.5 Hz), 8.09(1H, dd, J=7.2, 1.2 Hz), 8.10(1H, d, J=8.7 Hz),8.29(1H, t, J=6.3 Hz), 8.43(1H, d, J=8.4 Hz), 10.48(1H, s).

Example 43 (Compound 2-17); Yield: 53.5%

(DMSO-d₆): δ 2.81(6H, s), 3.86(2H, d, J=6.0 Hz), 6.52(2H, d, J=8.7 Hz),6.93(2H, d, J=8.7 Hz), 6.99(1H, d, J=7.5 Hz), 7.47(1H, dd, J=8.7, 7.8Hz), 7.52(1H, dd, J=8.4, 7.5 Hz), 8.06(1H, d, J=0.9 Hz), 8.09(1H, t,J=1.2 Hz), 8.20(1H, t, J=6.0 Hz), 8.40(1H, d, J=8.7 HZ).

Example 44 (Compound 2-18); Yield: 57.9%

(DMSO-d₆): δ 3.13(3H, s), 4.12(2H, d, J=6.3 Hz), 7.00(1H, d, J=7.8 Hz),7.37(2H, d, J=8.7 Hz), 7.47-7.52(2H, m), 7.67(2H, d, J=8.4 Hz), 8.05(1H,d, J=8.7 Hz), 8.07(1H, dd, J=7.2, 1.2 Hz), 8.39(1H, d, J=8.1 Hz),8.59(1H, t, J=6.3 Hz), 10.50(1H, s).

Example 45 (Compound 2-19); Yield: 73.6%

(DMSO-d₆): δ 4.43(2H, d, J=5.7 Hz), 7.00(1H, d, J=7.8 Hz), 7.33-7.41(3H,m), 7.43-7.50(2H, m), 7.52(1H, dd, J=8.4, 7.2 Hz), 7.80(1H, dd, J=7.2,1.8 Hz), 7.88(1H, d, J=7.5 Hz), 7.93(1H, d, J=8.4 Hz), 8.12(1H, d, J=8.7Hz), 8.14(1H, dd, J=7.2, 1.2 Hz), 8.43(1H, d, =8.1 Hz), 8.44(1H, t,J=5.4 Hz), 10.48(1H, s).

Example 46 (Compound 2-20); Yield: 55.0%

(DMSO-d₆): δ 1.93(3H, s), 3.98(2H, d, J=5.7 Hz), 5.73(1H, dd, J=2.7, 1.2Hz), 5.85(1H, d, J=2.7 Hz), 6.98(1H, d, J=7.2 Hz), 7.43-7.52(2H, m),8.01(1H, d, J=1.2 Hz), 8.04-8.05(1H, m), 8.35(1H, t, J=6.0 Hz), 8.40(1H,d, J=8.4 Hz), 10.44(1H, s).

Example 47 (Compound 2-21); Yield: 51.7%

(DMSO-d₆): δ 4.10(2H, d, J=6.0 Hz), 7.00(1H, d, J=7.5 Hz), 7.16(1H, t,J=6.0 Hz), 7.25(1H, d, J=7.8 Hz), 7.46-7.53(2H, m), 7.60(1H, t, J=7.5Hz), 8.08(2H, d, J=7.8 Hz), 8.34(1H, d, J=3.9 Hz), 8.40(1H, d, J=8.4Hz), 8.53(1H, t, J=6.0 Hz), 10.48(1H, s).

Example 48 (Compound 2-22); Yield: 57.6%

(DMSO-d₆): δ 4.17(2H, d, J=6.0 Hz), 7.01(1H, d, J=7.5 Hz), 7.13(1H, d,J=3.0 Hz), 7.15(1H, d, J=3.0 Hz), 7.46-7.52(3H, m), 7.55(1H, dd, J=8.4,7.2 Hz), 8.10(1H, d, J=8.7 Hz), 8.15(1H, dd, J=7.5, 1.2 Hz), 8.44(1H, d,J=8.4 Hz), 8.60(1H, t, J=6.0 Hz), 10.52(1H, s), 12.30(1H, s).

Example 49 (Compound 2-23); Yield: 67.0%

(CDCl₃): δ 0.68-0.81(2H, m), 1.01-1.11(3H, m), 1.26-1.34(1H, m),1.55-1.60(5H, m), 2.70(2H, t, J=6.6 Hz), 4.61(1H, t, J=6.6 Hz), 5.72(1H,s), 6.93(1H, dd, J=7.5, 6.0 Hz), 7.48(1H, dd, J=8.7, 7.5 Hz), 7.53(1H,dd, J=8.4, 7.8 Hz), 8.17(1H, d, J=8.7 Hz), 8.27(1H, dd, J=7.2, 1.2 Hz),8.52(1H, dd, J=8.4, 1.2 Hz).

Example 50 (Compound 2-24); Yield: 51.8%

(CDCl₃): δ 6.92-7.02(4H, m), 7.06-7.12(2H, m), 7.37(1H, dd, J=8.7, 7.5Hz), 7.46(1H, dd, J=8.7, 7.8 Hz), 8.16-8.23(2H, m), 8.49(1H, d, J=8.4Hz), 8.74(1H, s), 9.41(1H, bs).

Example 51 (Compound 2-25); Yield: 63.9%

(DMSO-d₆): δ 2.36(3H, s), 2.57(2H, t, J=7.2 Hz), 3.00-3.06(2H, m),7.00(2H, dd, J=8.1, 2.1 Hz), 7.10-7.18(3H, m), 7.37(2H, d, J=7.5 Hz),7.43(2H, d, J=8.7 Hz), 7.63(1H, dd, J=8.4, 7.2 Hz), 7.68(1H, t, J=8.4Hz), 7.83(2H, d, J=8.4 Hz), 8.12(1H, d, J=8.7 Hz), 8.13(1H, J=7.5 Hz),8.18(1H, t, J=6.0 Hz), 8.57(1H, d, J=8.7 Hz).

Example 52 (Compound 2-26); Yield: 57.8%

(CDCl₃): δ 1.33(3H, d, J=6.9 Hz), 4.38-4.47(1H, m), 4.98(1H, d, J=7.2Hz), 6.45(1H, bs), 6.87-6.92(3H, m), 6.95-7.03(3H, m), 7.36(1H, dd,J=8.4, 7.2 Hz), 7.42(1H, dd, J=8.7, 7.5 Hz), 8.07-8.13(2H, m), 8.41(1H,dt, J=8.1, 1.2 Hz)

Example 53 (Compound 2-27); Yield: 53.6%

(CDCl₃): δ 2.71(3H, s), 4.44(2H, s), 6.94(2H, d, J=7.5 Hz),7.21-7.33(5H, m), 7.49(1H, dd, J=8.7, 7.5 Hz), 7.55(1H, dd, J=8.7, 7.5Hz), 8.27(1H, dd, J=7.5, 1.2 Hz), 8.36(1H, d, J=8.7 Hz), 8.53-8.56(1H,m).

Example 54 Preparation of 5-acetyloxy-N-benzylnaphthalene-2-sulfonamide(Compound No. 3-1) (1) Preparation of5-(acetyloxy)naphthalene-2-sulfonyl chloride

This compound was prepared by the preparation method disclosed inTetrahedron, volume 48, No. 42, pp. 9207-9216 (published in 1992), andJapanese Patent Kokai Koho Sho 60-140240.

(2) Preparation of 5-acetyloxy-N-benzylnaphthalene-2-sulfonamide

Triethylamine (50 μl, 0.36 mmol) and 5-(acetyloxy)naphthalene-2-sulfonylchloride (84.9 mg, 0.30 mmol) were added to benzylamine (32.1 mg, 0.30mmol) dissolved in tetrahydrofuran (3 ml), and the mixture was stirredat room temperature for 30 minutes. The reaction mixture was poured intodiluted hydrochloric acid and extracted with ethyl acetate. After theorganic layer was washed with saturated brine, dried over anhydroussodium sulfate, the residue obtained by evaporation of the solvent underreduced pressure was purified by column chromatography on silica gel(eluent; n-hexane: ethyl acetate=2:1→1:1) to give the title compound asa light yellow white crystal (72.1 mg, 67.6%).

¹H-NMR(CDCl₃): δ 2.49(3H, s), 4.16(2H, d, J=6.3 Hz), 4.92(1H, t, J=6.0Hz), 7.16-7.26(5H, m), 7.43(1H, dd, J=7.8, 1.2 Hz), 7.61(1H, dd, J=8.1,7.8 Hz), 7.84(1H, d, J=8.4 Hz), 7.86(1H, dd, J=8.7, 1.8 Hz), 8.00(1H, d,J=8.7 Hz), 8.45(1H, d, J=2.1 Hz).

Example 55 to Example 68

The following compounds were prepared in the same manner as the methodof Example 54(2).

Example 55 (Compound 3-2); Yield: 88.5%

(DMSO-d₆): δ 2.49(3H, s), 4.10(2H, d, J=6.3 Hz), 7.34(1H, dd, J=8.4, 2.1Hz), 7.44(1H, d, J=8.4 Hz), 7.47(1H, d, J=2.4 Hz), 7.51(1H, d, J=7.5Hz), 7.70(1H, t, J=7.8 Hz), 7.86(1H, dd, J=8.7, 1.5 Hz), 8.08(1H, d,J=8.1 Hz), 8.12(1H, d, J=9.0 Hz), 8.44(1H, t, J=6.3 Hz), 8.48(1H, s).

Example 56 (Compound 3-3); Yield: 91.7%

(DMSO-d₆): δ 2.48(3H, s), 4.22(2H, d, J=6.3 Hz), 7.48-7.53(2H, m),7.66-7.72(2H, m), 7.85(1H, dd, J=8.7, 1.5 Hz), 7.97-8.00(1H, m),8.04-8.11(3H, m), 8.48(1H, d, J=1.5 Hz), 8.55(1H, t, J=6.3 Hz).

Example 57 (Compound 3-4); Yield: 91.3%

(CDCl₃): δ 1.23(9H, s), 2.49(3H, s), 4.14(2H, d, J=6.3 Hz), 4.94(1H, t,J=6.3 Hz), 7.09(2H, d, J=8.4 Hz), 7.21-7.26(2H, m), 7.42(1H, dd, J=7.8,0.9 Hz), 7.60(1H, dd, J=7.8, 7.5 Hz), 7.83(1H, d, J=8.7 Hz), 7.84(1H,dd, J=9.0, 1.8 Hz), 7.98(1H, d, J=9.3 Hz), 8.44(1H, d, J=2.1 Hz).

Example 58 (Compound 3-5); Yield: 92.9%

(DMSO-d₆): δ 2.48(3H, s), 4.15(2H, s), 7.46(2H, d, J=8.1 Hz), 7.50(1H,dd, J=7.5, 1.5 Hz), 7.58(2H, d, J=8.4 Hz), 7.69(1H, t, J=8.1 Hz),7.86(1H, dd, J=9.0, 1.8 Hz), 8.06(1H, d, J=8.1 Hz), 8.11(1H, d, J=8.7Hz), 8.47(2H, d, J=1.5 Hz).

Example 59 (Compound 3-6); Yield: 92.8%

(CDCl₃): δ 2.48(3H, s), 3.69(3H, s), 3.72(3H, s), 4.19(2H, d, J=6.6 Hz),5.20(1H, t, J=6.3 Hz), 6.64(2H, d, J=7.5 Hz), 6.77(1H, dd, J=8.7, 6.9Hz), 7.39(1H, dd, J=7.8, 1.2 Hz), 7.58(1H, dd, J=8.4, 7.2 Hz),7.77-7.81(2H, m), 7.90(1H, d, J=8.7 Hz), 8.35(1H, d, J=1.8 Hz).

Example 60 (Compound 3-7); Yield: 63.7%

(DMSO-d₆): δ 2.49(3H, s), 3.83(2H, d, J=6.3 Hz), 5.03(2H, s), 6.35(1H,d, J=7.5 Hz), 6.40(1H, d, J=7.2 Hz), 6.50(1H, s), 6.88(1H, t, J=7.5 Hz),7.51(1H, d, J=7.5 Hz), 7.70(1H, t, J=7.8 Hz), 7.90(1H, dd, J=8.7, 1.5Hz), 8.09-8.16(2H, m), 8.18(1H, t, J=6.0 HZ), 8.52(1H, d, J=1.8 Hz).

Example 61 (Compound 3-8); Yield: 65.8%

(DMSO-d₆): δ 4.50(3H, s), 4.46(2H, d, J=6.0 Hz), 7.37-7.45(2H, m),7.48-7.53(3H, m), 7.71(1H, t, J=7.8 Hz), 7.81(1H, d, J=7.8 Hz),7.87-7.93(2H, m), 8.05-8.14(3H, m), 8.34(1H, t, J=6.0 Hz), 8.56(1H, d,J=1.8 Hz).

Example 62 (Compound 3-9); Yield: 94.3%

(DMSO-d₆): δ 1.87(3H, s), 2.48(3H, s), 4.01(2H, d, J=6.0 Hz), 5.75(1H,dd, J=3.0, 1.2 Hz), 6.01(1H, d, J=3.0 Hz), 7.49(21, dd, J=7.2, 0.6 Hz),7.68(1H, t, J=7.8 Hz), 7.81(1H, dd, J=9.0, 1.8 Hz), 8.06(1H, d, J=8.1Hz), 8.08(1H, d, J=9.0 Hz), 8.29(1H, t, J=6.0 Hz), 8.43(1H, d, J=1.8Hz).

Example 63 (Compound 3-10); Yield: 99.5%

(DMSO-d₆): δ 2.48(3H, s), 4.14(2H, d, J=6.3 Hz), 7.16(1H, ddd, J=7.5,4.8, 1.2 Hz), 7.35(1H, d, J=7.8 Hz), 7.50(1H, dd, J=7.5, 1.2 Hz),7.63-7.72(2H, m), 7.87(1H, dd, J=9.0, 1.8 Hz), 8.07(1H, d, J=7.5 Hz),8.10(1H, d, J=8.7 Hz), 8.37(1H, ddd, J=4.8, 1.8, 0.9 Hz), 8.44(1H, t,J=6.3 Hz), 8.49(1H, d, J=1.5 Hz).

Example 64 (Compound 3-11); Yield: 59.6%

(DMSO-d₆): δ 0.73-0.86(2H, m), 1.06-1.13(3H, m), 1.33(1H, m),1.54-1.66(5H, m), 2.48(3H, s), 2.60(2H, t, J=6.3 Hz), 7.50(1H, dd,J=7.5, 0.9 Hz), 7.69(1H, t, J=8.1 Hz), 7.74(1H, t, J=6.0 Hz), 7.86(1H,dd, J=8.7, 1.8 Hz), 8.11(1H, d, J=7.2 Hz), 8.13(1H, d, J=8.7 Hz),8.49(1H, d, J=1.8 H).

Example 65 (Compound 3-12); Yield: 88.2%

(DMSO-d₆): δ 2.45(3H, 9), 7.00(1H, t, J=7.2 Hz), 7.11-7.14(2H, m),7.18-7.23 (2H, m), 7.49(1H, d, J=7.5 Hz), 7.67(1H, t, J=8.1 Hz),7.81(1H, dd, J=9.0, 1.5 Hz), 8.09(2H, t, J=9.0 Hz), 8.51(1H, d, J=1.5Hz), 10.46(1H, s).

Example 66 (Compound 3-13); Yield: 76.7%

(DMSO-d₆): δ 2.40(3H, s), 2.68(2H, t, J=7.5 Hz), 2.98-3.05(2H, m),7.12-7.25(5H, m), 7.50(1H, dd, J=7.5, 0.9 Hz), 7.69(1H, t, J=7.2 Hz),7.85(1H, dd, J=9.0, 1.8 Hz), 7.89(1H, t, J=5.7 Hz), 8.09-8.14(2H, m),8.50(1H, d, J=1.5 Hz).

Example 67 (Compound 3-14); Yield: 96.0%

(CD₃OD): δ 1.34(3H, d, J=7.2 Hz), 2.45(3H, s), 4.47(1H, q, J=6.9 Hz),6.86-6.92(1H, m), 6.94-6.99(2H, m), 7.02-7.06(2H, m), 7.38(1H, dd,J=7.8, 1.2 Hz), 7.57(1H, t, J=7.8 Hz), 7.70(1H, dd, J=8.7, 1.8 Hz),7.77(1H, d, J=8.1 Hz), 7.88(1H, d, J=9.0 Hz), 8.16(1H, d, J=1.8 Hz).

Example 68 (Compound 3-15); Yield: 87.2%

(DMSO-d₆): δ 2.50(3H, s), 2.61(3H, s), 4.22(2H, s), 7.31-7.40(5H, m),7.55(1H, d, J=7.5 Hz), 7.74(1H, t, J=7.8 Hz), 7.91(1H, dd, J=8.7, 1.5Hz), 8.18(1H, d, J=8.4 Hz), 8.19(1H, d, J=9.0 Hz), 8.64(1H, d, J=1.5Hz).

Example 69 Preparation of N-benzyl-5-hydroxynaphthalene-2-sulfonamide(Compound No. 4-1)

Ethanol (3 ml) and 2N aqueous sodium hydroxide (0.1 ml) were added to5-acetyloxy-N-benzylnaphthalene-2-sulfonamide (Compound No. 3-1; 62.0mg, 0.17 mmol), and the mixture was stirred at room temperature for 5minutes. The reaction mixture was poured into diluted hydrochloric acidand extracted with ethyl acetate. After the organic layer was washedwith saturated brine, dried over anhydrous sodium sulfate, the residueobtained by evaporation of the solvent under reduced pressure waspurified by column chromatography on silica gel (eluent; n-hexane: ethylacetate=1:1) to give the title compound as a yellow white crystal (53.3mg, 100%).

¹H-NMR(DMSO-d₆): δ 4.01(2H, d, J=6.3 Hz), 7.04(1H, dd, J=7.5, 1.2 Hz),7.18-7.31(5H, m), 7.46(1H, dd, J=8.1, 7.5 Hz), 7.55(1H, d, J=8.4 Hz),7.75(1H, dd, J=8.7, 1.8 Hz), 8.21(1H, t, J=6.3 Hz), 8.27(1H, d, J=9.0Hz), 8.32(1H, d, J=1.8 Hz), 10.45(1H, s).

Example 70 to Example 83

The following compounds were prepared in the same manner as the methodof Example 69. The compounds prepared in Example 55 to Example 68 wereused as the law materials.

Example 70 (Compound 4-2); Yield: 69.5%

(DMSO-d₆): δ 4.08(2H, s), 7.04(1H, dd, J=7.5, 1.2 Hz), 7.36(1H, dd,J=8.4, 2.4 Hz), 7.43-7.49(3H, m), 7.54(1H, d, J=7.8 Hz), 7.74(1H, dd,J=8.7, 1.5 Hz), 8.26-8.34(3H, m), 10.48(1H, s).

Example 71 (Compound 4-3); Yield: 87.8%

(DMSO-d₆): δ 4.20(2H, d, J=6.0 Hz), 7.03(1H, d, J=7.2 Hz), 7.42-7.55(3H,m), 7.72(2H, t, J=7.5 Hz), 7.99(1H, d, J=5.7 Hz), 8.10(1H, s), 8.25(1H,d, J=9.0 Hz), 8.28(1H, s), 8.45(1H, t, 6.0 Hz), 10.45(1H, s).

Example 72 (Compound 4-4); Yield: 99.4%

(CDCl₃): δ 1.24(9H, s), 4.25(2H, d, J=6.0 Hz), 4.74(1H, t, J=6.0 Hz),5.83(1H, s), 6.98(1H, dd, J=7.5, 0.9 Hz), 7.10(2H, d, J=8.4 Hz),7.25(2H, d, J=8.4 Hz), 7.42(1H, dd, J=8.1, 7.8 Hz), 7.52(1H, d, J=8.4Hz), 7.79(1H, dd, J=8.7, 2.1 Hz), 8.31(1H, d, J=8.7 Hz), 8.37(1H, d,J=2.1 Hz).

Example 73 (Compound 4-5); Yield: 92.4%

(DMSO-d₆): δ 4.13(1H, d, J=3.3 Hz), 7.04(1H, dd, J=7.5, 1.2 Hz),7.43-7.49(3H, m), 7.53(1H, d, J=7.8 Hz), 7.60(2H, d, J=8.4 Hz), 7.74(1H,dd, J=9.0, 1.8 Hz), 8.27(1H, d, J=9.0 Hz), 8.29(1H, d, J=1.8 Hz),8.36(1H, bs), 10.46(1H, bs)

Example 74 (Compound 4-6); Yield: 67.3%

(DMSO-d₆): δ 3.61(3H, s), 3.74(3H, s), 3.99(2H, d, J=6.3 Hz),6.86-6.91(2H, m), 6.70(1H, dd, J=8.1, 7.2 Hz), 7.04(1H, dd, J=7.2, 1.2Hz), 7.46(1H, dd, J=8.4, 7.2 Hz), 7.55(1H, d, J=8.1 Hz), 7.76(1H, dd,J=9.0, 2.1 Hz), 8.07(1H, t, J=6.3 Hz), 8.28(1H, d, J=8.7 Hz), 8.31(1H,d, J=1.8 Hz), 10.45(1H, s).

Example 75 (Compound 4-7); Yield: 88.9%

(DMSO-d₆): δ 3.82(2H, d, J=6.3 Hz), 5.05(2H, s), 6.36(1H, d, J=7.5 Hz),6.40-6.43(1H, m), 6.51(1H, s), 6.90(1H, t, J=7.8 Hz), 7.04(1H, dd,J=7.8, 1.2 Hz), 7.46(1H, t, J=7.8 Hz), 7.56(1H, d, J=8.1 Hz), 7.77(1H,dd, J=8.7, 1.5 Hz), 8.07(1H, t, J=6.3 Hz), 8.29(1H, d, J=8.7 Hz),8.33(1H, d, J=1.8 Hz), 10.46(1H, s).

Example 76 (Compound 4-8); Yield: 95.0%

(DMSO-d₆): δ 4.44(2H, d, J=6.0 Hz), 7.05(1H, d, J=7.5 Hz), 7.38-7.47(3H,m), 7.50-7.58(3H, m), 7.80-7.84(2H, m), 7.91(1H, dd, J=6.3, 3.6 Hz),8.08(1H, dd, J=6.3, 3.6 Hz), 8.23(1H, t, J=6.0 Hz), 8.30(1H, d, J=9.0Hz), 8.39(1H, d, J=1.8 Hz), 10.48(1H, s).

Example 77 (Compound 4-9); Yield: 86.7%

(DMSO-d₆): δ 1.94(3H, s), 3.98(2H, d, J=6.0 Hz), 5.80(1H, d, J=1.8 Hz),6.01(1H, d, J=2.7 Hz), 7.02(1H, d, J=7.5 Hz), 7.45(1H, t, J=7.5 Hz),7.53(1H, d, J=8.1 Hz), 7.70(1H, dd, J=9.0, 1.8 Hz), 8.17(1H, t, J=6.0Hz), 8.24(1H, d, J=8.7 Hz), 8.25(1H, s), 1H, s).

Example 78 (Compound 4-10); Yield: 90.5%

(DMSO-d₆): δ 4.12(2H, d, J=6.0 Hz), 7.04(1H, dd, J=7.5, 0.9 Hz),7.19(1H, dd, J=6.6, 4.8 Hz), 7.38(1H, d, J=8.1 Hz), 7.46(1H, t, J=8.1Hz), 7.55(1H, d, J=8.4 Hz), 7.70(1H, td, J=7.8, 1.8 Hz), 7.76(1H, dd,J=9.0, 1.8 Hz), 8.27(1H, d, J=9.0 Hz), 8.32(1H, d, J=1.8 Hz), 8.35(1H,t, J=6.3 Hz), 8.40(1H, dd, J=4.8, 0.9 Hz), 10.47(1H, s).

Example 79 (Compound 4-11); Yield: 79.7%

(DMSO-d₆): δ 0.73-0.88(2H, m), 1.03-1.15(3H, m), 1.38(1H, m),1.50-1.69(5H, m), 2.59(2H, t, J=6.3 Hz), 7.03(1H, d, J=6.9 Hz), 7.45(1H,t, J=7.5 Hz), 7.56(1H, d, H=8.1), 7.65(1H, t, J=6.0 Hz), 7.74(1H, dd,J=8.7, 1.8 Hz), 8.28(1H, d, J=8.7 Hz), 8.30(1H, s), 10.46(1H, s).

Example 80 (Compound 4-12); Yield: 94.3%

(DMSO-d₆): δ 6.96-7.03(2H, m), 7.10-7.13(2H, m), 7.17-7.22(2H, m),7.43(1H, t, J=8.1 Hz), 7.52(1H, d, J=8.4 Hz), 7.69(1H, dd, J=9.0, 1.8Hz), 8.23(1H, d, J=9.0 _(Hz),) 8.30(1H, d, J=1.5 Hz), 10.35(1H, s),10.47(1H, s).

Example 81 (Compound 4-13); Yield: 94.5%

(DMSO-d₆): δ 2.67(2H, t, J=7.5 Hz), 2.96-3.03(2H, m), 7.03(1H, d, J=7.5Hz), 7.12-7.26(5H, m), 7.45(1H, t, J=7.8 Hz), 7.56(1H, d, J=8.4 Hz),8.28(1H, d, J=8.7 Hz), 8.31(1H, d, J=1.2 Hz), 10.47(1H, s).

Example 82 (Compound 4-14); Yield: 89.8%

(DMSO-d₆): δ 1.19(3H, d, J=6.9 Hz), 4.40(1H, m), 7.01(1H, dd, J=6.9, 1.8Hz), 7.07(1H, tt, J=6.9, 1.8 Hz), 7.10-7.23(4H, m), 7.39-7.48(2H, m),7.66(1H, dd, J=8.7, 2.1 Hz), 8.18(1H, d, J=8.7 Hz), 8.19(1H, d, J=2.7Hz), 8.26(1H, d, J=8.1 Hz), 10.41(1H, s).

Example 83 (Compound 4-15); Yield: 89.8%

(DMSO-d₆): δ 2.59(3H, s), 4.20(2H, s), 7.08(1H, dd, J=8.7, 0.9 Hz),7.28-7.40(5H, m), 7.50(1H, t, J=8.4 Hz), 7.64(1H, d, J=8.1 Hz), 7.79(1H,dd, J=8.7, 1.5 Hz), 8.36(1H, d, J=8.7 Hz), 8.43(1H, d, J=1.8 Hz),10.54(1H, s).

Example 84 Preparation of5-acetylamino-N-benzylnaphthalene-2-sulfonamide (Compound No. 5-1) (1)Preparation of 5-(acetylamino)naphthalene-2-sulfonyl chloride

This compound was prepared by the preparation method disclosed in theU.S. Pat. No. 5,378,715.

(2) Preparation of 5-acetylamino-N-benzylnaphthalene-2-sulfonamide

5-(Acetylamino)naphthalene-2-sulfonyl chloride (280 mg, 0.987 mmol) wasadded to benzylamine (127 mg, 1.19 mmol) and triethylamine (0.17 ml,1.22 mmol) dissolved in tetrahydrofuran (3.0 ml), and the mixture wasstirred at room temperature for 1 hour. Water (10 ml) was added to thereaction solution, and after the mixture was stirred for 10 minutes, theresulting solid was collected. The solid was washed with water andisopropyl ether to give the title compound as a light pink solid (296mg, 84.6%).

¹H-NMR(DMSO-d₆): δ 2.21(3H, s), 4.03(2H, d, J=6.3 Hz), 7.18-7.26(5H, m),7.64(1H, t, J=8.1 Hz), 7.83-7.88(2H, m), 7.98(1H, d, J=7.8 Hz), 8.25(1H,d, J=9.0 Hz), 8.28(1H, t, J=6.3 Hz), 8.44(1H, d, J=1.8 Hz), 10.06(1H,s).

Example 85 to Example 87

The following compounds were prepared in the same manner as the methodof Example 84(2).

Example 85 (Compound 5-2); Yield: 85.7%

(DMSO-d₆): δ 1.18(9H, s), 2.20(3H, s), 3.98(2H, d, J=6.3 Hz), 7.13(2H,d, J=8.4 Hz), 7.24(2H, d, J=8.1 Hz), 7.62(1H, t, J=7.8 Hz),7.80-7.86(2H, m), 7.94(1H, d, J=7.8 Hz), 8.21(1H, t, J=6.0 Hz), 8.22(1H,d, J=9.3 Hz), 8.38(1H, d, J=1.8 Hz), 10.04(1H, s).

Example 86 (Compound 5-3); Yield: 80.7%

(DMSO-d₆): δ 2.21(3H, s), 3.61(3H, s), 3.73 '3H, s), 4.00(2H, d, J=6.0H), 6.86-6.90(2H, m), 6.97(1H, dd, J=8.4, 7.5 Hz), 7.64(1H, t, J=7.8Hz), 7.84-7.89(2H, m), 7.97(1H, d, J=8.4 Hz), 8.13(1H, t, J=6.0 Hz),8.25(1H, d, J=9.0 Hz), 8.43(1H, d, J=1.8 Hz), 10.06(1H, s).

Example 87 (Compound 5-4); Yield: 63.9%

(DMSO-d₆): δ 1.19(3H, d, J=6.9 Hz), 2.20(3H, s), 4.36-4.46(1H, m),7.03-7.08(1H, m), 7.12-7.23(4H, m), 7.60(1H, t, J=8.1 Hz), 7.78(1H, dd,J=9.0, 2.1 Hz), 7.83(1H, d, J=7.5 Hz), 7.88(1H, d, J=7.8 Hz), 8.18(1H,d, J=8.7 Hz), 8.28(1H, d, J=1.5 Hz), 8.32(1H, d, J=8.1 Hz), 10.01(1H,s).

Example 88 Preparation of 5-amino-N-benzylnaphthalene-2-sulfonamide(Compound No. 6-1)

5-Acetylamino-N-benzylnaphthalene-2-sulfonamide (compound No. 5-1; 175mg, 0.494 mmol) was suspended to a mixed solvent of 1-propanol (3.0 ml)and water (1.5 ml). Concentrated hydrochloric acid (1.5 ml) was added tothe suspension and the mixture was refluxed for 1 hour. After cooling toroom temperature, the separated crystal was collected and washed with1-propanol and isopropyl ether to give the title compound as a lightyellow crystal (128 mg, 74.4%).

¹ H-NMR(DMSO-d₆): δ 4.03(2H, d, J=6.0 Hz), 7.17-7.27(5H, m), 7.47(1H, d,J=6.3 Hz), 7.59(1H, t, J=7.8 Hz), 7.84-7.90(2H, m), 8.26(1H, d, J=9.0Hz), 8.32(1H, t, J=6.3 Hz), 8.42(1H, d, J=1.5 Hz).

Example 89 to Example 91

The following compounds were prepared in the same manner as the methodof Example 88. The compounds prepared in Example 85 to Example 87 wereused as the law materials.

Example 89 (Compound 6-2); Yield: 74.1%

(DMSO-d₆): δ 1.19(9H, s), 3.99(2H, d, J=6.0 Hz), 7.15(2H, d, J=8.7 Hz),7.22-7.26(2H, m), 7.48(1H, d, J=7.2 Hz), 7.58(t, J=7.8 Hz),7.83-7.90(2H, m), 8.25(1H, d, J=7.8 Hz), 8.28(1H, t, J=6.0 Hz), 8.37(1H,d, J=1.8 Hz).

Example 90 (Compound 6-3); Yield: 80.5%

(DMSO-d₆): δ 3.61(3H, s), 3.74(3H, s), 4.00(1H, d, J=5.7 Hz),6.87-6.91(2H, m), 6.96(1H, d, J=7.2 Hz), 7.45(1H, d, J=7.5 Hz), 7.59(1H,t, J=7.8 Hz), 7.83-7.90(2H, m), 8.17(1H, t, J=6.0 Hz), 8.26(1H, d, J=9.3Hz), 8.41(1H, d, J=1.5 Hz).

Example 91 (Compound 6-4); Yield: 73.3%

(DMSO-d₆): δ 1.19(3H, d, J=7.2 Hz), 4.37-4.47(1H, m), 7.02-7.08(1H, m),7.12-7.23(4H, m), 7.37(1H, d, J=7.2 Hz), 7.53(1H, t, J=7.8 Hz), 7.70(1H,d, J=8.1 Hz), 7.76(1H, dd, J=8.7, 1.8 Hz), 8.16(1H, d, J=9.3 Hz),8.24(1H, d, J=1.8 Hz), 8.34(1H, d, J=8.4 Hz).

Example 92 Preparation of6-acetylamino-N-benzylnaphthalene-1-sulfonamide (Compound No. 7-1) (1)Preparation of 6-(acetylamino)naphthalene-1-sulfonyl chloride

This compound was prepared by the preparation method disclosed in theU.S. Pat. No. 5,378,715.

(2) Preparation of 6-acetylamino-N-benzylnaphthalene-1-sulfonamide

6-(Acetylamino)naphthalene-1-sulfonyl chloride (280 mg, 0.987 mmol) wasadded to a solution of benzylamine (127 mg, 1.19 mmol) and triethylamine(0.17 ml, 1.22 mmol) in tetrahydrofuran (3.0 ml), and the mixture wasstirred at room temperature for 1 hour. Water (10 ml) was added to thereaction solution, and after the mixture was stirred for 10 minutes, theresulting solid was collected. The solid was washed with water and amixed solvent of ethyl acetate/isopropyl ether (1/1) to give the titlecompound as a white solid (284 mg, 81.1%).

¹H-NMR(DMSO-d₆): δ 2.13(3H, s), 4.01(1H, d, J=6.3 Hz), 7.13-7.20(5H, m),7.54(1H, t, J=7.8 Hz), 7.71(1H, dd, J=9.3, 2.1 Hz), 7.97(1H, dd, J=7.5,1.2 Hz), 8.08(1H, d, J=8.4 Hz), 8.43-8.47(2H, m), 8.58(1H, d, J=9.3 Hz),10.30(1H, s).

Example 93 and Example 94

The following compounds were prepared in the same manner as the methodof Example 92(2).

Example 93 (Compound 7-2); Yield: 88.4%

(DMSO-d₆): δ 1.20(9H, s), 2.13(3H, s), 3.96(2H, d, J=5.7 Hz), 7.01(2H,d, J=8.1 Hz), 7.15(2H, d, J=8.4 Hz), 7.52(1H, t, J=7.8 Hz), 7.70(1H, dd,J=9.3, 2.1 Hz), 7.94(1H, dd, J=7.2, 0.9 Hz), 8.05(1H, d, J=7.8 Hz),8.37(1H, t, J=6.0 Hz), 8.42(1H, d, J=1.8 Hz), 8.56(1H, d, J=9.3 Hz),10.29(1H, s).

Example 94 (Compound 7-3); Yield: 84.8%

(DMSO-d₆): δ 2.13(3H, s), 3.55(3H, s), 3.74(3H, s), 4.00(2H, d, J=6.0Hz), 6.78(1H, dd, J=5.7, 3.9 Hz), 6.86-6.89(2H, m), 7.55(1H, t J=7.8Hz), 7.71(1H, dd, J=9.3, 2.1 Hz), 7.98(1H, dd, J=7.5, 1.2 Hz), 8.09(1H,d, J=8.7 Hz), 8.29(1H, t, J=6.0 Hz), 8.44(1H, d, J=1.8 Hz), 8.60(1H, d,J=9.0 Hz), 10.30(1H, s).

Example 95 Preparation of 6-amino-N-benzylnaphthalene-1-sulfonamidehydrochloride (Compound No. 8-1)

6-Acetylamino-N-benzylnaphthalene-1-sulfonamide (compound No. 7-1; 188mg, 0.530 mmol) was suspended to a mixed solvent of 1-propanol (3.0 ml)and water (1.5 ml). Concentrated hydrochloric acid (1.5 ml) was added tothe suspension and the mixture was refluxed for 1 hour. After cooling toroom temperature, the separated crystal was collected and washed with1-propanol and isopropyl ether to give the title compound as a lightyellow crystal (118 mg, 63.8%).

¹H-NMR(DMSO-d₆): δ 4.02(2H, d, J=6.3 Hz), 7.13-7.20(5H, m), 7.49(1H, dd,J=9.0, 2.4 Hz), 7.57(1H, t, J=7.8 Hz), 7.69(1H, d, J=1.8 Hz), 7.99(1H,dd, J=7.5, 1.2 Hz), 8.53(1H, t, J=6.0 Hz), 8.63(1H, d, J=9.0 Hz).

Example 96 and Example 97

The following compounds were prepared in the same manner as the methodof Example 88. The compounds prepared in Example 93 and Example 94 wereused as the law materials.

Example 96 (Compound 8-2); Yield: 35.4%

(DMSO-d₆): δ 1.21(9H, s), 3.97(2H, d, J=6.0 Hz), 7.04(2H, d, J=8.1 Hz),7.17(2H, d, J=8.4 Hz), 7.42(1H, dd, J=8.7, 2.4 Hz), 7.52(1H, t, J=7.8Hz), 7.56(1H, bs), 7.9(1H, dd, J=7.2, 0.9 Hz), 8.04(1H, d, J=8.4 Hz),8.42(1H, t, J=6.0 Hz), 8.58(1H, d, J=9.3 Hz).

Example 97 (Compound 8-3); Yield: 39.8%

(DMSO-d₆): δ 3.55(3H, s), 3.74(3H, s), 4.01(2H, d, J=6.0 Hz), 6.79(1H,dd, J=6.0, 3.3 Hz), 6.86-6.90(2H, m), 7.45(1H, dd, J=9.3, 2.1 Hz),7.58(1H, t, J=7.8 Hz), 7.64(1H, bs), 7.98(1H, dd, J=7.5, 0.9 Hz),8.10(1H, d, J=8.4 Hz), 8.35(1H, t, J=6.0 Hz), 8.63(1H, d, J=9.3 Hz).

Example 98 Preparation of6-acetylamino-N-benzylnaphthalene-2-sulfonamide (Compound No. 9-1) (1)Preparation of 6-(acetylamino)naphthalene-2-sulfonyl chloride

This compound was prepared by the preparation method disclosed in theU.S. Pat. No. 5,378,715.

(2) Preparation of 6-acetylamino-N-benzylnaphthalene-2-sulfonamide

6-(Acetylamino)naphthalene-2-sulfonyl chloride (280 mg, 0.987 mmol) wasadded to a solution of benzylamine (127 mg, 1.19 mmol) and triethylamine(0.17 ml, 1.22 mmol) in tetrahydrofuran (3.0 ml), and the mixture wasstirred at room temperature for 1 hour. Water (10 ml) was added to thereaction solution, and after the mixture was stirred for 10 minutes, theresulting solid was collected. The solid was washed with water and amixed solvent of ethyl acetate/isopropyl ether (1/1) to give the titlecompound as a white solid (307 mg, 87.7%).

¹H-NMR(DMSO-d₆): δ 2.14(3H, s), 4.00(2H, d, J=6.3 Hz), 7.17-7.25(5H, m),7.68(1H, dd, J=8.7, 1.8 Hz), 7.76(1H, dd, J=8.4, 1.8 Hz), 7.99(1H, d,J=9.0 Hz), 8.07(1H, d, J=9.0 Hz), 8.16(1H, t, J=6.3 Hz), 8.33(1H, d,J=1.8 Hz), 8.42(1H, d, J=1.5 Hz), 10.33(1H, s).

Example 99 and Example 100

The following compounds were prepared in the same manner as the methodof Example 98(2).

Example 99 (Compound 9-2); Yield: 84.7%

(DMSO-d₆): δ 1.19(9H, s), 2.13(3H, s), 3.96(2H, d, J=6.0 Hz), 7.13(2H,d, J=8.7 Hz), 7.22(2H, d, 8.4 Hz), 7.67(1H, dd, J=8.7, 1.8 Hz), 7.73(1H,dd, J=8.4, 1.8 Hz), 7.96(1H, d, J=9.0 Hz), 8.04(1H, d, J=9.0 Hz),8.13(1H, t, J=6.3 Hz), 8.28(1H, d, J=1.8 Hz), 8.41(1H, d, J=1.5 Hz),10.32(1H, s).

Example 100 (Compound 9-3); Yield: 88.5%

(DMSO-d₆): δ 2.13(3H, s), 3.60(3H, s), 3.74(3H, s), 3.99(2H, d, J=6.0Hz), 6.85-6.90(2H, m), 6.96(1H, dd, J=8.4, 7.2 Hz), 7.68(1H, dd, J=8.7,1.8 Hz), 7.77(1H, dd, J=8.7, 1.8 Hz), 7.98-8.08(3H, m), 8.32(1H, d,J=1.2 Hz), 8.42(1H, d, J=1.2 Hz), 10.33(1H, s).

Example 101 Preparation of 6-amino-N-benzylnaphthalene-2-sulfonamidehydrochloride (Compound No. 10-1)

6-Acetylamino-N-benzylnaphthalene-2-sulfonamide (compound No. 9-1; 185mg, 0.522 mmol) was suspended to a mixed solvent of 1-propanol (3.0 ml)and water (1.5 ml). Concentrated hydrochloric acid (1.5 ml) was added tothe suspension and the mixture was refluxed for 1 hour. After cooling toroom temperature, the separated crystal was collected and washed with1-propanol and isopropyl ether to give the title compound as a lightyellow crystal (135 mg, 74.2%).

¹H-NMR(DMSO-d₆): δ 3.99(2H, d, J=5.7 Hz), 7.12-7.25(5H, m), 7.35(1H, d,J=9.0 Hz), 7.46(1H, s), 7.75(1H, d, J=8.7 Hz), 7.93(1H, d, J=8.7 Hz),8.04(1H, d, J=8.7 Hz), 8.18(1H, t, J=6.3 Hz), 8.31(1H, s).

Example 102 and Example 103

The following compounds were prepared in the same manner as the methodof Example 88. The compounds prepared in Example 99 and Example 100 wereused as the law materials.

Example 102 (Compound 10-2); Yield: 78.1%

(DMSO-d₆): δ 1.19(9H, s), 3.99(2H, d, J=6.0 Hz), 7.15(2H, d, J=8.7 Hz),7.22-7.26(2H, m), 7.48(1H, d, J=7.2 Hz), 7.58(1H, t, J=7.8 Hz),7.83-7.90(2H, m), 8.25(2H, d, J=8.4 Hz), 8.37(1H, d, J=1.8 Hz).

Example 103 (Compound 10-3); Yield: 67.3%

(DMSO-d₆): δ 3.60(3H, s), 3.73(3H, s), 3.98(2H, d, J=5.4 Hz),6.86-6.99(3H, m), 7.36(1H, d, J=8.7 Hz), 7.47(1H, s), 7.76(1H, dd,J=8.7, 1.8 Hz), 7.94(1H, d, J=8.7 Hz), 8.02-8.06(2H, m), 8.31(1H, s)

Example 104 Preparation of 5-amino-N-benzylnaphthalene-1-carboxamide(Compound No. 11-1) (1) Preparation of 5-nitronaphthalene-1-carboxylicacid

This compound was prepared by the preparation method disclosed inTetrahedron, volume 49, No. 17, pp. 3655-3663 (published in 1993).

(2) Preparation of N-benzyl-5-nitronaphthalene-1-carboxamide

Triethylamine (0.16 ml, 1.15 mmol) and ethyl chloroformate (0.11 ml,1.115 mmol) were added to a suspension of5-nitronaphthalene-1-carboxylic acid (250 mg, 1.15 mmol) and anhydroustetrahydrofuran (3 ml) under ice cooling, and the mixture was stirredfor 0.5 hour. Benzylamine (0.13 ml, 1.20 mmol) was added to the reactionmixture and the mixture was stirred at room temperature for 6 hours.Water was added to the reaction solution, and after the mixture wasstirred for 10 minutes, the resulting precipitate was collected. Theprecipitate was washed with water and isopropyl ether, and dried to givethe title compound as a light brown solid (189 mg, 53.5%).

¹H-NMR(DMSO-d₆): δ 4.57(2H, d, J=6.0 Hz), 7.26-7.31(1H, m),7.34-7.44(4H, m), 7.77(1H, dd, J=8.4, 7.8 Hz), 7.84-7.85(2H, m),8.33(1H, dd, J=7.5, 0.9 Hz), 8.36-8.41(1H, m), 8.55(1H, d, J=8.7 Hz),9.28(1H, t, J=6.0 Hz).

(3) Preparation of 5-amino-N-benzylnaphthalene-1-carboxamide

5% Palladium on carbon (14 mg) was added to a suspension ofN-benzyl-5-nitronaphthalene-1-carboxamide (128.0 mg, 0.418 mmol) inmethanol (2.5 ml). The mixture was stirred at room temperature for 2hours, under hydrogen atmosphere. After the palladium on carbon wasfiltered off, the filtrate was concentrated. The residue was solidifiedby a mixture of isopropyl ether: ethyl acetate (1:1), and the resultingsolid was washed with isopropyl ether and dried to give the titlecompound as a light yellow solid (102 mg, 88.7%).

¹H-NMR(DMSO-d₆): δ 4.51(2H, d, J=6.0 Hz), 5.77(2H, s), 6.70(1H, dd,J=7.5, 1.2 Hz), 7.19-7.40(8H, m), 7.49(1H, dd, J=7.2, 1.2 Hz), 8.15(1H,d, J=8.1 Hz), 8.95(1H, t, J=6.0 Hz).

Example 105 Preparation of5-amino-N-[4-(tert-butyl)benzyl]naphthalene-1-carboxamide (Compound No.11-2) (1) Preparation ofN-[4-(tert-butyl)benzyl]-5-nitronaphthalene-1-carboxamide

Using 5-nitronaphthalene-1-carboxylic acid (197 mg, 0.907 mmol) and4-tert-butylbenzylamine (107 mg, 0.998 mmol), the same operation as theExample 104(2) gave the title compound as a light yellow solid (140 mg,42.6%).

¹H-NMR(CDCl₃): δ 1.32(9H, s), 4.72(1H, d, J=5.4 Hz), 6.29(1H, s),7.34(2H, d, J=8.7 Hz), 7.42(2H, d, J=8.4 Hz), 7.64(1H, dd, J=8.7, 7.2Hz), 7.68(1H, dd, J=8.7, 7.2 Hz), 7.74(1H, dd, J=7.2, 1.5 Hz), 8.24(1H,dd, J=7.5, 1.2 Hz), 8.60(1H, dt, J=7.5, 1.5 Hz), 8.71(1H, dt, J=8.4, 1.2Hz).

(2) Preparation of5-amino-N-[4-(tert-butyl)benzyl]naphthalene-1-carboxamide

Using N-[4-(tert-butyl)benzyl]-5-nitronaphthalene-1-carboxamide (140 mg,0.386 mmol), the same operation as the Example 104(3) gave the titlecompound as a yellow solid (97 mg, 75.8%).

¹H-NMR(DMSO-d₆): δ 1.28(9H, s), 4.47(2H, d, J=6.0 Hz), 6.71(1H, dd,J=7.5, 0.9 Hz), 7.22(1H, dd, J=8.4, 7.5 Hz), 7.30(2H, d, J=8.4 Hz),7.33-7.41(2H, m), 7.38(2H, d, J=8.4 Hz), 7.48(1H, dd, J=6.9, 1.2 Hz),8.14(1H, d, J=8.7 Hz), 8.91(1H, t, J=6.0 Hz).

Example 106 Preparation of5-amino-N-(2,3-dimethoxybenzyl)naphthalene-1-carboxamide (Compound No.11-3) (1) Preparation ofN-(2,3-dimethoxybenzyl)-5-nitronaphthalene-1-carboxamide

Using 5-nitronaphthalene-1-carboxylic acid (250 mg, 1.15 mmol) and2,3-dimethoxybenzylamine (0.18 ml, 1.20 mmol), the same operation as theExample 104(2) gave the title compound as a gray white solid (232 mg,55.0%).

¹H-NMR(DMSO-d₆): δ 3.81(3H, s), 3.82(3H, s), 4.58(2H, d, J=6.0 Hz),6.98-7.00(2H, m), 7.09(1H, dd, J=8.7, 6.9 Hz), 7.70(1H, dd, 8.4, 7.8Hz), 7.83-7.85(2H, m), 8.33(1H, dd, J=7.5, 1.2 Hz), 8.36-8.40(1H, m),8.55(1H, dt, J=8.4, 0.9 Hz), 9.15(1H, t, J=6.0 Hz).

(2) Preparation of5-amino-N-(2,3-dimethoxybenzyl)naphthalene-1-carboxamide

Using N-(2,3-dimethoxybenzyl)-5-nitronaphthalene-1-carboxamide (168 mg,0.459 mmol), the same operation as the Example 104(3) gave the titlecompound as a light pink solid (147 mg, 95.4%).

¹H-NMR(DMSO-d₆): δ 3.79(3H, s), 3.81(3H, s), 4.52(2H.d.J=6.3 Hz),5.78(2H, s), 6.70(1H, dd, J=7.2, 0.6 Hz), 6.95-6.99(2H, m), 7.06(1H, d,J=7.5 Hz), 7.22(1H, t, J=8.7 Hz), 7.33(1H, d, J=8.4 Hz), 7.38(1H, dd,J=8.4, 7.2 Hz), 7.49(1H, dd, J=7.2, 0.6 Hz), 8.15(1H, d, J=8.1 Hz),8.82(1H, t, J=5.7 Hz 9).

Test Example

By using aforementioned synthetic compounds, effects on proliferation ofJurkat cells by sole administration and inhibitory effects on cellproliferation by administration in combination with bleomycin wereexamined. Materials and methods are as follows. Jurkat cells obtainedfrom Dainippon Pharmaceutical Co. Ltd. were inoculated at about 10,000cells per well in a 96 well culture plate, and incubated in 10% bovinefetal serum (Irvine Scientific) supplemented with RPMI1640 (ICN) mediumin 5% CO₂ incubator at 37° C. For the culture, each compound was addedalone, or the culture was further added with bleomycin (Wako) to give aconcentration of 5 μg/ml or 10 μg/ml. 36 hours after the incubation, thenumber of living cells was counted by the MTS method.

More specifically, 20 μl of CellTiter96™ AQueous One Solution (Promega)was added per one well, and after the cells were incubated foradditional one hour, an absorbance at 490 nm was measured by using amicroplate reader. The same culture added with DMSO as a solvent atfinal concentration of 0.25% was used as a control. The number of cellsin the control was considered as 100% survival rate, and for eachcompound, survival rates by sole administration or a combinedadministration were calculated. Treatments solely with bleomycin at 5μg/ml or 10 μg/ml gave about 5 to 10% of decrease in the survival ratesof the Jurkat cells. Whilst, when the compound of the present inventioncoexisted, the survival rates of the Jurkat cells by bleomycin at 5μg/ml or 10 μg/ml were remarkably decreased. The results are shown inthe following table. In the table, ┌++┘ indicates observation ofremarkable enhancement, ┌+┘ indicates moderated enhancement.

Compound Number Activity 1-1  ++ 1-2  + 1-3  ++ 1-5  ++ 1-6  ++ 1-7  ++1-9  ++ 1-11 ++ 1-12 + 1-13 + 1-15 + 1-16 + 1-17 ++ 1-19 ++ 1-20 +1-23 + 1-24 ++ 1-25 + 1-26 ++ 1-27 + 2-3  ++ 2-7  ++ 2-8  + 2-9  +2-11 + 2-13 + 2-19 ++ 2-23 + 2-25 + 3-1  + 3-4  ++ 3-5  + 3-9  + 4-1  +4-3  + 4-4  ++ 4-5  + 4-6  + 4-7  + 4-8  + 4-13 + 6-2  + 6-3  + 8-2  +11-1  +

INDUSTRIAL APPLICABILITY

In cancer treatments based on the mode of action of DNA injury, themedicaments of the present invention have inhibitory actions againstprotein kinases, which are activated in the cancer cells suffered fromthe DNA injury, to kill said cancer cells. The medicaments of thepresent invention thus enhance the effect of a cancer therapy based onthe mode of action of DNA injury and reduce a dose of an anticanceragent and/or radiation. Therefore, the medicaments can reduce sideeffects resulting from the cancer therapy.

1. A composition, which comprises as an active ingredient a substanceselected from a compound represented by the following general formula(I) or a pharmacologically acceptable salt thereof:

wherein one of R¹ and R² represents hydrogen atom and the otherrepresents the formula —X-A wherein A represents a hydrogen atom, ahydrocarbon-carbonyl group, or a hydrocarbon-sulfonyl group, Xrepresents an oxygen atom or NH; one of R³ and R⁴ represents hydrogenatom and the other represents the following formula:

wherein Y represents a sulfonyl group or a carbonyl group, R⁵ representsa phenyl group which may be substituted with one or more substituentsselected from a halogen atom, a nitro group, an alkyl group, ahalogenated alkyl group, a hydroxyl group, an alkoxy group, analkylenedioxy group, an amino group, an N,N-di(alkyl)-amino group, andan alkyl-sulfonyl group,  a naphthyl group which may be substituted,  afuryl group which may be substituted,  a pyridyl group which may besubstituted,  a benzimidazolyl group which may be substituted, or  acycloalkyl group, Z represents a single bond or a C₁ to C₄ alkylenegroup, R⁶ hydrogen atom or a C₁ to C₆ alkyl group, with the followingprovisos: a compound represented by the following formula:

wherein each of A, Z, R⁵ and R⁶ has the same meaning as that definedabove is excluded; when one of R¹ and R² is the formula —O—A, A is ahydrogen atom, Y is a carbonyl group, Z is a single bond, and R⁶ ishydrogen atom, then R⁵ is a phenyl group which may be substituted withone or more substituents selected from a halogen atom, a nitro group, analkyl group, a halogenated alkyl group, an alkoxy group, analkylenedioxy group, an amino group, an N,N-di(alkyl)-amino group, andan alkyl-sulfonyl group,  a naphthyl group which may be substituted,  afuryl group which may be substituted,  a pyridyl group which may besubstituted,  a benzimidazolyl group which may be substituted, or  acycloalkyl group; when R² is the formula —NH-A, A is a hydrogen atom, Yis a sulfonyl group, Z is a C₁ alkylene group, and R⁶ is hydrogen atom,then R⁵ is a phenyl group which may be substituted with one or moresubstituents selected from a halogen atom, a nitro group, an alkylgroup, a halogenated alkyl group, a hydroxyl group, an alkoxy group, analkylenedioxy group, an amino group, an N,N-di(alkyl)-amino group, andan alkyl-sulfonyl group,  a naphthyl group which may be substituted,  afuryl group which may be substituted,  a pyridyl group which may besubstituted,  a benzimidazolyl group which may be substituted, or  acycloalkyl group; when R¹ is the formula —NH-A, A is a hydrogen atom, R³is a hydrogen atom, Y is a sulfonyl group, Z is a C₁ alkylene group, andR⁶ is hydrogen atom, then R⁵ is a phenyl group which may be substitutedwith one or more substituents selected from a halogen atom, a nitrogroup, an alkyl group, a halogenated alkyl group, a hydroxyl group, analkoxy group, an alkylenedioxy group, an amino group, anN,N-di(alkyl)-amino group, and an alkyl-sulfonyl group,  a naphthylgroup which may be substituted,  a furyl group which may be substituted, a pyridyl group which may be substituted,  a benzimidazolyl group whichmay be substituted, or  a cycloalkyl group; and when one of R¹ and R² isthe formula —NH-A, A is a hydrogen atom, Y is a sulfonyl group, Z is asingle bond, and R⁶ is hydrogen atom, then R⁵ is a phenyl group which issubstituted with one or more substituents selected from a halogen atom,a nitro group, an alkyl group, a halogenated alkyl group, a hydroxylgroup, an alkoxy group, an alkylenedioxy group, an amino group, anN,N-di(alkyl)-amino group, and an alkyl-sulfonyl group,  a naphthylgroup which may be substituted,  a furyl group which may be substituted, a pyridyl group which may be substituted, or  a benzimidazolyl groupwhich may be substituted.
 2. The composition according to claim 1,wherein Z is a methylene group, an ethylene group, an ethane-1,1-diylgroup, a propane-1,3-diyl group, a propane-1,2-diyl group, apropane-2,2-diyl group, or a butane-1,4-diyl group.
 3. The compositionaccording to claim 1, wherein Y is a sulfonyl group.
 4. The compositionaccording to claim 1, wherein R¹ is a group represented by the formula—X-A wherein A represents a hydrogen atom, a hydrocarbon-carbonyl group,or a hydrocarbon-sulfonyl group, X represents an oxygen atom or NH, andR² is a hydrogen atom.
 5. The composition according to claim 1, furthercomprising an anticancer agent selected from bleomycin, adriamycin,cisplatin, cyclophosphamide, mitomycin C, and derivatives thereof. 6.The composition according to claim 1, which is a specific inhibitor of aprotein kinase and/or an analogous enzyme thereof.
 7. A compoundrepresented by the general formula (I) or a pharmacologically acceptablesalt thereof according to claim 1, provided that the following compoundis excluded:


8. A compound selected from the following compounds or apharmacologically acceptable salt thereof:N-Benzyl-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(2,6-Difluorobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(2,4-Dichlorobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(3-Nitrobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(4-Nitrobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene--1-sulfonamide;N-(2-Methylbenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-[4-(tert-Butyl)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-[2-(Trifluoromethyl)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-[4-(Trifluoromethyl)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(3,4-Dihydroxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(2-Methoxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(3-Methoxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(2,3-Dimethoxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(3,5-Dimethoxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(3,4-Methylenedioxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(3-Aminobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-[4-(Dimethylamino)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-[4-(Methanesulfonyl)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(1-Naphthylmethyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-[(5-Methylfuran-2-yl)methyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-[(Pyridin-2-yl)methyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-[(Benzimidazol-2-yl)methyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-Cyclohexylmethyl-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-Phenyl-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(2-Phenethyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(1-Phenethyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-Benzyl-N-methyl-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-Benzyl-5-hydroxynaphthalene-1-sulfonamide;N-(2,6-Difluorobenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(2,4-Dichlorobenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(3-Nitrobenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(4-Nitrobenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(2-Methylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-[4-(tert-Butyl)benzyl]-5-hydroxynaphthalene-1-sulfonamide;N-[2-(Trifluoromethyl)benzyl]-5-hydroxynaphthalene-1-sulfonamide;N-[4-(Trifluoromethyl)benzyl]-5-hydroxynaphthalene-1-sulfonamide;N-(3,4-Dihydroxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(2-Methoxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(3-Methoxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(2,3-Dimethoxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(3,5-Dimethoxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(3,4-Methylenedioxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(3-Aminobenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-[4-(Dimethylamino)benzyl]-5-hydroxynaphthalene-1-sulfonamide;N-[4-(Methanesulfonyl)benzyl]-5-hydroxynaphthalene-1-sulfonamide;N-(1-Naphthylmethyl)-5-hydroxynaphthalene-1-sulfonamide;N-[(5-Methylfuran-2-yl)methyl]-5-hydroxynaphthalene-1-sulfonamide;N-[(Pyridin-2-yl)methyl]-5-hydroxynaphthalene-1-sulfonamide;N-[(Benzimidazol-2-yl)methyl]-5-hydroxynaphthalene-1-sulfonamide;N-Cyclohexylmethyl-5-hydroxynaphthalene-1-sulfonamide;N-Phenyl-5-hydroxynaphthalene-1-sulfonamide;N-(2-Phenethyl)-5-hydroxynaphthalene-1-sulfonamide;N-(1-Phenethyl)-5-hydroxynaphthalene-1-sulfonamide;N-Benzyl-N-methyl-5-hydroxynaphthalene-1-sulfonamide;5-Acetyloxy-N-benzylnaphthalene-2-sulfonamide;5-Acetyloxy-N-(2,4-dichlorobenzyl)naphthalene-2-sulfonamide;5-Acetyloxy-N-(3-nitrobenzyl)naphthalene-2-sulfonamide;5-Acetyloxy-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide;5-Acetyloxy-N-[4-(trifluoromethyl)benzyl]naphthalene-2-sulfonamide;5-Acetyloxy-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide;5-Acetyloxy-N-(3-aminobenzyl)naphthalene-2-sulfonamide;5-Acetyloxy-N-(1-naphthylmethyl)naphthalene-2-sulfonamide;5-Acetyloxy-N-[(5-methylfuran-2-yl)methyl]naphthalene-2-sulfonamide;5-Acetyloxy-N-[(pyridin-2-yl)methyl]naphthalene-2-sulfonamide;5-Acetyloxy-N-(cyclohexylmethyl)naphthalene-2-sulfonamide;5-Acetyloxy-N-phenylnaphthalene-2-sulfonamide;5-Acetyloxy-N-(2-phenethyl)naphthalene-2-sulfonamide;5-Acetyloxy-N-(1-phenethyl)naphthalene-2-sulfonamide;5-Acetyloxy-N-benzyl-N-methylnaphthalene-2-sulfonamide;N-Benzyl-5-hydroxynaphthalene-2-sulfonamide;N-(2,4-Dichlorobenzyl)-5-hydroxynaphthalene-2-sulfonamide;N-(3-Nitrobenzyl)-5-hydroxynaphthalene-2-sulfonamide;N-[4-(tert-Butyl)benzyl]-5-hydroxynaphthalene-2-sulfonamide;N-[4-(Trifluoromethyl)benzyl]-5-hydroxynaphthalene-2-sulfonamide;N-(2,3-Dimethoxybenzyl)-5-hydroxynaphthalene-2-sulfonamide;N-(3-Aminobenzyl)-5-hydroxynaphthalene-2-sulfonamide;N-(1-Naphthylmethyl)-5-hydroxynaphthalene-2-sulfonamide;N-[(5-Methylfuran-2-yl)methyl]-5-hydroxynaphthalene-2-sulfonamide;N-[(Pyridin-2-yl)methyl]-5-hydroxynaphthalene-2-sulfonamide;N-(Cyclohexylmethyl)-5-hydroxynaphthalene-2-sulfonamide;N-Phenyl-5-hydroxynaphthalene-2-sulfonamide;N-(2-Phenethyl)-5-hydroxynaphthalene-2-sulfonamide;N-(1-Phenethyl)-5-hydroxynaphthalene-2-sulfonamide;N-Benzyl-N-methyl-5-hydroxynaphthalene-2-sulfonamide;5-Acetylamino-N-benzylnaphthalene-2-sulfonamide;5-Acetylamino-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide;5-Acetylamino-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide;5-Acetylamino-N-benzyl-N-methylnaphthalene-2-sulfonamide;5-Amino-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide;5-Amino-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide;5-Amino-N-benzyl-N-methylnaphthalene-2-sulfonamide;6-Acetylamino-N-[4-(tert-butyl)benzyl]naphthalene-1-sulfonamide;6-Acetylamino-N-(2,3-dimethoxybenzyl)naphthalene-1-sulfonamide;6-Amino-N-[4-(tert-butyl)benzyl]naphthalene-1-sulfonamide;6-Amino-N-(2,3-dimethoxybenzyl)naphthalene-1-sulfonamide;6-Acetylamino-N-benzylnaphthalene-2-sulfonamide;6-Acetylamino-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide;6-Acetylamino-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide;6-Amino-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide;6-Amino-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide;5-Amino-N-benzylnaphthalene-1-carboxamide;5-Amino-N-[4-(tert-butyl)benzyl]naphthalene-1-carboxamide; and5-Amino-N-(2,3-dimethoxybenzyl)naphthalene-1-carboxamide.
 9. Acomposition which comprises as an active ingredient a substance selectedfrom a compound represented by the general formula (I) or apharmacologically acceptable salt thereof according to claim
 7. 10. Thecomposition according to claim 1, wherein R⁵ is a substituted phenylgroup.
 11. The composition according to claim 1, wherein the compound isselected from the following compounds:N-Benzyl-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(2,6-Difluorobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(2,4-Dichlorobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(3-Nitrobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(4-Nitrobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(2-Methylbenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-[4-(tert-Butyl)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-[2-(Trifluoromethyl)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-[4-(Trifluoromethyl)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(3,4-Dihydroxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(2-Methoxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(3-Methoxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(2,3-Dimethoxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(3,5-Dimethoxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(3,4-Methylenedioxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(3-Aminobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-[4-(Dimethylamino)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-[4-(Methanesulfonyl)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(1-Naphthylmethyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-[(5-Methylfuran-2-yl)methyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-[(Pyridin-2-yl)methyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1sulfonamide;N-[(Benzimidazol-2-yl)methyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-Cyclohexylmethyl-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-Phenyl-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(2-Phenethyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-(1-Phenethyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-Benzyl-N-methyl-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;N-Benzyl-5-hydroxynaphthalene-1-sulfonamide;N-(2,6-Difluorobenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(2,4-Dichlorobenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(3-Nitrobenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(4-Nitrobenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(2-Methylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-[4-(tert-Butyl)benzyl]-5-hydroxynaphthalene-1-sulfonamide;N-[2-(Trifluoromethyl)benzyl]-5-hydroxynaphthalene-1-sulfonamide;N-[4-(Trifluoromethyl)benzyl]-5-hydroxynaphthalene-1-sulfonamide;N-(3,4-Dihydroxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(2-Methoxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(3-Methoxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(2,3-Dimethoxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(3,5-Dimethoxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(3,4-Methylenedioxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-(3-Aminobenzyl)-5-hydroxynaphthalene-1-sulfonamide;N-[4-(Dimethylamino)benzyl]-5-hydroxynaphthalene-1-sulfonamide;N-[4-(Methanesulfonyl)benzyl]-5-hydroxynaphthalene-1-sulfonamide;N-(1-Naphthylmethyl)-5-hydroxynaphthalene-1-sulfonamide;N-[(5-Methylfuran-2-yl)methyl]-5-hydroxynaphthalene-1-sulfonamide;N-[(Pyridin-2-yl)methyl]-5-hydroxynaphthalene-1-sulfonamide;N-[(Benzimidazol-2-yl)methyl]-5-hydroxynaphthalene-1-sulfonamide;N-Cyclohexylmethyl-5-hydroxynaphthalene-1-sulfonamide;N-Phenyl-5-hydroxynaphthalene-1-sulfonamide;N-(2-Phenethyl)-5-hydroxynaphthalene-1-sulfonamide;N-(1-Phenethyl)-5-hydroxynaphthalene-1-sulfonamide;N-Benzyl-N-methyl-5-hydroxynaphthalene-1-sulfonamide;5-Acetyloxy-N-benzylnaphthalene-2-sulfonamide;5-Acetyloxy-N-(2,4-dichlorobenzyl)naphthalene-2-sulfonamide;5-Acetyloxy-N-(3-nitrobenzyl)naphthalene-2-sulfonamide;5-Acetyloxy-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide;5-Acetyloxy-N-[4-(trifluoromethyl)benzyl]naphthalene-2-sulfonamide;5-Acetyloxy-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide;5-Acetyloxy-N-(3-aminobenzyl)naphthalene-2-sulfonamide;5-Acetyloxy-N-(1-naphthylmethyl)naphthalene-2-sulfonamide;5-Acetyloxy-N-[(5-methylfuran-2-yl)methyl]naphthalene-2-sulfonamide;5-Acetyloxy-N-[(pyridin-2-yl)methyl]naphthalene-2-sulfonamide;5-Acetyloxy-N-(cyclohexylmethyl)naphthalene-2-sulfonamide;5-Acetyloxy-N-phenylnaphthalene-2-sulfonamide;5-Acetyloxy-N-(2-phenethyl)naphthalene-2-sulfonamide;5-Acetyloxy-N-(1-phenethyl)naphthalene-2-sulfonamide;5-Acetyloxy-N-benzyl-N-methylnaphthalene-2-sulfonamide;N-Benzyl-5-hydroxynaphthalene-2-sulfonamide;N-(2,4-Dichlorobenzyl)-5-hydroxynaphthalene-2-sulfonamide;N-(3-Nitrobenzyl)-5-hydroxynaphthalene-2-sulfonamide;N-[4-(tert-Butyl)benzyl]-5-hydroxynaphthalene-2-sulfonamide;N-[4-(Trifluoromethyl)benzyl]-5-hydroxynaphthalene-2-sulfonamide;N-(2,3-Dimethoxybenzyl)-5-hydroxynaphthalene-2-sulfonamide;N-(3-Aminobenzyl)-5-hydroxynaphthalene-2-sulfonamide;N-(1-Naphthylmethyl)-5-hydroxynaphthalene-2-sulfonamide;N-[(5-Methylfuran-2-yl)methyl]-5-hydroxynaphthalene-2-sulfonamide;N-[(Pyridin-2-yl)methyl]-5-hydroxynaphthalene-2-sulfonamide;N-(Cyclohexylmethyl)-5-hydroxynaphthalene-2-sulfonamide;N-Phenyl-5-hydroxynaphthalene-2-sulfonamide;N-(2-Phenethyl)-5-hydroxynaphthalene-2-sulfonamide;N-(1-Phenethyl)-5-hydroxynaphthalene-2-sulfonamide;N-Benzyl-N-methyl-5-hydroxynaphthalene-2-sulfonamide;5-Acetylamino-N-benzylnaphthalene-2-sulfonamide;5-Acetylamino-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide;5-Acetylamino-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide;5-Acetylamino-N-benzyl-N-methylnaphthalene-2-sulfonamide;5-Amino-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide;5-Amino-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide;5-Amino-N-benzyl-N-methylnaphthalene-2-sulfonamide;6-Acetylamino-N-[4-(tert-butyl)benzyl]naphthalene-1-sulfonamide;6-Acetylamino-N-(2,3-dimethoxybenzyl)naphthalene-1-sulfonamide;6-Amino-N-[4-(tert-butyl)benzyl]naphthalene-1-sulfonamide;6-Amino-N-(2,3-dimethoxybenzyl)naphthalene-1-sulfonamide;6-Acetylamino-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide;6-Acetylamino-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide;6-Amino-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide;6-Amino-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide;5-Amino-N-benzylnaphthalene-1-carboxamide;5-Amino-N-[4-(tert-butyl)benzyl]naphthalene-1-carboxamide; and5-Amino-N-(2,3-dimethoxybenzyl)naphthalene-1-carboxamide.
 12. Thecomposition according to claim 1, wherein the compound isN-[4-(tert-butyl)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide.13. The compound according to claim 7 or a pharmacologically acceptablesalt thereof, wherein A is a hydrogen atom, an acetyl group, or apara-toluenesulfonyl group.
 14. The composition according to claim 1,wherein A is a hydrogen atom, an alkyl-carbonyl group, or anaryl-sulfonyl group which may be substituted with one or more alkylgroups.
 15. The composition according to claim 1, wherein A is ahydrogen atom, an acetyl group, or a para-toluenesulfonyl group.
 16. Thecomposition according to claim 1, wherein R⁵ is a phenyl group,2,6-difluorophenyl group, 2,4-dichlorophenyl group, 3-nitrophenyl group,4-nitrophenyl group, 2-methylphenyl group, 4-(tert-butyl)phenyl group,2-(trifluoromethyl)phenyl group, 4-(trifluoromethyl)phenyl group,3,4-dihydroxyphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group,2,3-dimethoxyphenyl group, 3,5-dimethoxyphenyl group,3,4-methylenedioxyphenyl group, 3-aminophenyl group,4-(dimethylamino)phenyl group, 4-methanesulfonylphenyl group, 1-naphthylgroup, 5-methylfuran-2-yl group, pyridin-2-yl group, benzimidazol-2-ylgroup, or cyclohexyl group.
 17. The compound according to claim 7 or apharmacologically acceptable salt thereof, wherein Z is a methylenegroup, an ethylene group, an ethane-1,1-diyl group, a propane-1,3-diylgroup, a propane-1,2-diyl group, a propane-2,2-diyl group, or abutane-1,4-diyl group.
 18. The compound according to claim 7 or apharmacologically acceptable salt thereof, wherein A is a hydrogen atom,an alkyl-carbonyl group, or an aryl-sulfonyl group which may besubstituted with one or more alkyl groups.
 19. The compound according toclaim 7 or a pharmacologically acceptable salt thereof, wherein R⁵ is aphenyl group, 2,6-difluorophenyl group, 2,4-dichlorophenyl group,3-nitrophenyl group, 4-nitrophenyl group, 2-methylphenyl group,4-(tert-butyl)phenyl group, 2-(trifluoromethyl)phenyl group,4-(trifluoromethyl)phenyl group, 3,4-dihydroxyphenyl group,2-methoxyphenyl group, 3-methoxyphenyl group, 2,3-dimethoxyphenyl group,3,5-dimethoxyphenyl group, 3,4-methylenedioxyphenyl group, 3-aminophenylgroup, 4-(dimethylamino)phenyl group, 4-methanesulfonylphenyl group,1-naphthyl group, 5-methylfuran-2-yl group, pyridin-2-yl group,benzimidazol-2-yl group, or cyclohexyl group.
 20. The compositionaccording to claim 9, which is a specific inhibitor of a protein kinaseand/or an analogous enzyme thereof.
 21. The composition according toclaim 9, which is used for reducing a side effect resulting from acancer therapy based on a mode of action of DNA injury.